Amide compounds and use thereof

ABSTRACT

An amide compound given by formula [I]:  
                 
 
     wherein R 1  represents a C1-C10 haloalkyl and so on, R2 represents a hydrogen and so on, X represents an oxygen or sulfur, Y represents an oxygen or sulfur, Ar represents an aromatic group, A represents an ethylene and so on, and Z 1  and Z 2  represent alkyl, alkoxy and so on,  
     and a fungicide containing it as an active ingredient.

TECHNICAL FIELD

[0001] The present invention relates to amide compounds and their use for fungicide.

BACKGROUND ARTS

[0002] The present invention provides an amide compound which can be more excellent fungicidal active ingredient, though various fungicides for controlling plant diseases have been known hitherto.

DISCLOSURE OF THE INVENTION

[0003] The present invention provides an amide compound given by formula [I]:

[0004] wherein R¹ represents a C1-C10 haloalkyl group, C2-C10 haloalkonyl group, C3-C10 haloalkynyl group, C3-C8 halocycloalkyl group or C3-C10 alkynyl group; R² represents a hydrogen atom or C1-C3 alkyl group (namely, methy, ethyl, propyl and isopropyl); X represents an oxygen atom or sulfur atom; Y represents an oxygen atom or sulfur atom; Ar represents an aromatic group; A represents an ethylene group or trimethylene group, said ethylene group and trimethylene group may be substituted by one or more selected from halogen atom, amino group, hydroxy group, cyano group, nitro group, C1-C6 alkyl group, C3-C6 cycloalkyl group, C3-C6 cycloalkenyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group, C2-C6 (alkoxycarbonyl) group and tri(C1-C6 alkyl)silyl group; Z¹ and Z² are the same or different and represents a halogen atom (chlorine, bromine, fluorine, iodine), C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C6 cycloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C2-C6 (alkoxyalkoxy) group, C4-C6 (cycloalkylalkoxy) group, C3-C6 alkenyloxy group, C3-C6 haloalkenyloxy group, C3-C6 alkynyloxy group, C3-C6 haloalkynyloxy group, C3-C6 cycloalkoxy group, C3-C6 cycloalkenyloxy group, cyano C1-C5 alkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group (C1-C5 alkoxy)carbonyl group, phenoxy group, benzyloxy group, hydroxy group or cyano group, the benzene ring of said phenyl group and benzyloxy group may be substituted by one or more selected from halogen atom (chlorine, bromine, fluorine, iodine) C1-C6 alkyl group, C1-C6 alkoxy group, trifluoromethyl group, amino group and nitro group; and Z¹ and Z² may represents C2-C6 alkylenedioxy group together, (heeinafter, referred to as the present compound) and fungicide comprising it as an active ingredient.

[0005] In the present invention, examples of the C1-C10 haloalkyl group for R¹ include fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, chlorofluoromethyl, bromodifluoromethyl, trichloromethyl, dichlorobromomethyl, 1,1,2,2,2-pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl and 2-fluoroethyl; examples of the C2-C10 haloalkenyl group include 2-fluorovinyl, 2,2-difluorovinul, trifluorovinyl, 3-chloropropenyl, 3,3-dichloropropenyl, 3-fluoropropenyl, 3,3-difluoropropenyl, 2,3,3-trifluoropropenyl and 10-fluoro-2-decenyl; examples of the C3-C10 haloalkynyl group include 3-fluoro-2-propynyl, 3-chloro-2-propynyl, 3-bromo-2-propynyl, 3-iodo-2-propynyl, 4-fluoro-2-butynyl, 4,4-difluoro-2-butynyl, 4,4,4-trifluoro-2-butynyl and 4-chloro-2-butynyl; examples of the C3-C8 halocycloalkyl group include 2,2-difluorocyclopropyl, 2,3,4-trifluorocyclobutyl, 2,5-dichlorocyclopentyl, 4,4-difluorocyclohexy and 2-chlorocycloheptyl; and examples of the C3-C10 alkynyl group include 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 5-pentynyl and 7-octynyl. Among them, C1-C3 haloalkyl group, C2-C3 haloalkenyl group, C3-C5-haloalkynyl group, C3-C6 halocycloalkyl group and C3-C8 alkynyl group are preferable, and especialy fluoromethyl, difluoromethyl, trifluoromethyl and 2-propynyl are more preferable for R¹.

[0006] In the present invention, examples of the aromatic group for Ar include aromatic hydrocarbyl groups such as phenyl, naphthyl (1-naphthyl, 2-naphthyl) and so on; and aromatic heterocyclic groups such as thienyl (2-thienyl, 3-thienyl), furyl (2-furyl, 3-furyl), pyrrolyl (1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), pyrazolyl (1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), imidazolyl (1-imidazolyl, 2-imidazolyl, 4-imidazolyl), triazolyl (1-triazolyl, 4-triazolyl), tetrazolyl (1-tetrazolyl, 5-tetrazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), isothiazolyl (3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), thiadiazolyl (e.g. 1,2,5-thiadiazol-4-yl, 1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-5-yl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl), benzofuryl (2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5-benzofuryl, 6-benzofuryl, 7-benzofuryl), benzothienyl (2-benzothienyl, 3-benzothienyl, 4-benzothienyl, 5-benzothienyl, 6-benzothienyl, 7-benzothienyl), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), benzothiazolyl (2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl), benzopyrazolyl (1-benzopyrazolyl, 2-benzopyrazolyl, 3-benzopyrazolyl, 4-benzopyrazolyl, 5-benzopyrazolyl, 6-benzopyrazolyl, 7-benzopyrazolyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), pyrazolopyrimidinyl, imidazopyrimidinyl, thiophenopyrimidinyl, thiazolopyrimidinyl, pyrazolopyridyl, imidazopyridyl, thiophenopyridyl, thiazolopyridyl and so on; and said aromatic hydrocarbyl group and aromatic heterocyclic group may be substituted. Typical examples of the substituents include halogen (chlorine, bromine, fluorine, iodine), amino, hydroxy, cyano, nitro, C1-C10 alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 1-methylpropyl, pentyl, 1-methylbutyl, 1-ethylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1,2-dimethylbutyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 1-ethylpentyl, 3,3-dimethylbutyl, heptyl, 3,7-dimethyloctyl), C1-C10 haloalkyl (e.g. trifluoromethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl), cyano C1-C9 alkyl (e.g. cyanomethyl, 1-cyanoethyl, 2-cyanoethyl, 3-cyanopropyl, 5-cyanohexyl), C2-C10 alkenyl (e.g. vinyl, 1-propenyl, 2-propenyl, 1-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3,3-dimethyl-1-butenyl, 4-pentenyl, 5-hexenyl), C2-C10 haloalkenyl (e.g. 2-fluorovinyl, 3-chloro-2-propenyl, 3,3-dichloro-2-propenyl, 2-fluoro-1-propenyl, 3,3,3-trifluoro-1-propenyl, 4-chloro-3-butenyl, 2-chloro-3-methyl-1-butenyl, 2-fluoro-5-hexenyl), C2-C10 alkynyl (e.g. ethynyl, 1-propynyl, 2-propynyl, 1-methyl-2-propynyl, 1-ethyl-2-propynyl, 1-butynyl, 3,3-dimethyl-1-butynyl, 3-butynyl, 4-pentynyl, 5-hexynyl), C2-C10 haloalkynyl (e.g. 2-fluoroethynyl, 2-chloroethynyl, 3-chloro-2-propynyl, 4-fluoro-3-butynyl, 5-chloro-4-pentynyl, 6-bromo-5-hexynyl), C3-C6 cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), C3-C6 cycloalkenyl (e.g. 2-cyclopentenyl, 2-cyclohexenyl), C1-C10 alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, pentyloxy), C1-C10 haloalkoxy (e.g. trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy), C3-C10 alkenyloxy (e.g. 2-propenyloxy, 1-methyl-2-propenyloxy, 1-ethyl-2-propenyloxy, 2-butenyloxy, 3-butenyloxy, 2,2-dimethyl-3-butenyloxy, 4-pentenyloxy, 5-hexenyloxy), C3-C10 haloalkenyloxy (e.g. 3-chloro-2-propenyloxy, 3,3-dichloro-2 -propenyloxy, 2-fluoro-1-propenyloxy, 3,3,3-trifluoro-1-propenyloxy, 4-chloro-3-butenyloxy, 2-chloro-3-methyl-1-butenyloxy, 2-fluoro-5-hexenyloxy), C3-C10 alkynyloxy (e.g. 2-propynyloxy, 1-methyl-2-propynyloxy, 1-ethyl-2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 4-pentynyloxy, 5-hexynyloxy), C3-C10 haloalkynyloxy (e.g. 3-chloro-2-propynyloxy, 3-fluoro-2-propynyloxy, 4-fluoro-3-butynyloxy, 5-chloro-4-pentynyloxy, 6-bromo-5-hexynyloxy), C3-C10 cycloalkoxy (e.g. cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cyclooctyloxy), cyano C1-C9 alkoxy (e.g. cyanomethoxy, 1-cyanoethoxy, 2-cyanoethoxy, 3-cyanopropoxy, 5-cyanohexyloxy), C1-C10 alkylthio (e.g. methylthio, ethylthio, propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio, hexylthio), C1-C10 haloalkylthio (e.g. trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio), C2-C10 (alkoxycarbonyl) (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl), tri(C1-C6 alkyl)silyl (e.g. trimethylsilyl, triethylsilyl), C3-C5 alkylene (e.g. trimethylene, tetramethylene, pentamethylene) and methylenedioxy. Among them, preferred Ar's are 4-methylphenyl group, 4-ethylphenyl group, 4-methoxyphenyl group, 4-chlorophenyl group, 4-trifluoromethylphenyl group, 3,4-tetramethylenephenyl group (5,6,7,8-tetrahydronaphthalen-2-yl group), 3,4-trimethylenephenyl group (indan-5-yl group) and 2-naphthyl group.

[0007] In the present invention, the ethylene group (—CH₂CH₂—) and trimethylene group for A may be substituted by at least one selected from halogen (chlorine, bromine, fluorine, iodine), amino, hydroxy, cyano, nitro, C1-C6 alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, t-butyl), C3-C6 cycloalkyl (e.g. cyclopropyl, cyclopentyl, cyclohexyl), C3-C6 cycloalkenyl, C1-C6 alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, pentyloxy), C1-C6 haloalkoxy (e.g. trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy), C1-C6 alkylthio (e.g. methylthio, ethylthio, propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio, hexylthio), C1-C6 haloalkylthio (e.g. trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio), C2-C6 (alkoxycarbonyl) (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl) and (C1-C6 alkyl)silyl (e.g. trimethylsilyl, triethylsilyl). Among them, ethylene (—CH₂CH₂—) is preferable for A.

[0008] In the present invention, examples of the C1-C6 alkyl group for Z¹ and Z² include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, 1-methylbutyl, 1-ethylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl and 3,3-dimethylbutyl; examples of the C1-C6 haloalkyl group include trifluoromethyl, 2,2,2-trifluoroethyl and 1,1,2,2-tetrafluoroethyl; examples of the C2-C6 alkenyl group include vinyl, 2-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 4-methyl-3- butenyl, 4-pentenyl and 5-hexenyl; C2-C6 alkynyl group include ethynyl, 2-propynyl, 1-methyl-2-propynyl, 1-ethyl-2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-butynyl, 2-pentynyl and 4,4-dimethyl-2-pentynyl; examples of the C3-C6 cycloalkyl group include cyclopropyl, cyclopentyl and cyclohexyl; examples of the C1-C6 alkoxy group include methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy and pentyloxy; examples of the C1-C6 haloalkoxy group include trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy and 1,1,2,2-tetrafluoroethoxy; examples of the C2-C6 (alkoxyalkoxy) group include methoxymethoxy, 2-methoxyethoxy, ethoxymethoxy and isopropoxymethoxy; examples of the C4-C6 (cycloalkylalkoxy) group include cyclopropylmethyl; examples of the C3-C6 alkenyloxy group include 2-propenyloxy, 1-methyl-2-propenyloxy, 2-methyl-2-propenyloxy, 2-butenyloxy, 3-butenyloxy, 3-methyl-2-butenyloxy, 4-methyl-3- butenyloxy, 4-pentenyloxy and 5-hexenyloxy; examples of the C3-C6 haloalkenyloxy group include 2-chloro-2-propenyloxy, 3-fluoro-2- propenyloxy, 3-chloro-2-propenyloxy, 3-bromo-2-propenyloxy, 3,3-dichloro-2-propenyloxy, 2,3, 3-trifluoro-2-propenyloxy, 4-chloro-2-butenyloxy, 4-chloro-3-butenyloxy and 3-chloro-3-butenyloxy; examples of the C3-C6 alkynyloxy group include 2-propynyloxy, 1-methyl-2-propynyloxy, 1-ethyl-2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 1-methyl-2-butynyloxy, 2-pentynyloxy, 4-pentynyloxy and 4,4-dimethyl-2-pentynyloxy; examples of the C3-C6 haloalkynyloxy group include 3-fluoro-2-propynyloxy, 3-chloro-2-propynyloxy, 3-bromo-2-propynyloxy, 3-chloro-1-methyl-2-propynyloxy, 4,4,4-trifluoro-2-butynyloxy, 4-chloro-3-butynyloxy and 5-chloro-4-pentynyloxy; examples of the C3-C6 cycloalkoxy group include cyclopropoxy, cyclopentyloxy and cyclohexyloxy; examples of the C3-C6 cycloalkenyloxy group include cyclopentenyloxy and cyclohexenyloxy; examples of the cyano C1-C5 alkoxy group include cyanomethoxy, 1-cyanoethoxy and 2-cyanoethoxy; examples of the C1-C6 alkylthio group include methylthio, ethylthio, propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio and hexylthio; examples of the C1-C6 haloalkylthio group include trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio and 1,1,2,2-tetrafluoroethylthio; examples of the (C1-C5 alkoxy)carbonyl group include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and pentyloxycarbonyl; examples of the optionally substituted phenoxy group include phenoxy, 4-chlorophenoxy, 4-methylphenoxy, 4-methoxyphenoxy and 4-trifluoromethylphenoxy; examples of the optionally substituted benzyloxy group include benzyloxy, 4-chlorobenzyloxy, 4-methylbenzyloxy, 4-methoxybenzyloxy and 4-trifluoromethylbenzyloxy; and examples of the C2-C6 alkylenedioxy group include ethylenedioxy, propylenedioxy and trimethylenedioxy. Among them, preferable are methoxy for Z¹ and methoxy and 2-propynyloxy for Z².

[0009] In the present compounds, there exist (E) and (Z) isomers based on C═C double bond bonded with Ar and X, and the present invention include each isomer and mixtures thereof.

[0010] In the present compounds, the compounds having excellent efficacy for controlling plant diseases are exemplified by N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2 -(4-methylphenyl)acrylamide, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-[2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8 -tetrahydronaphthalen-2-yl)acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide and N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-chlorophenyl) acrylamide.

[0011] The present compounds can be produced, for example, by the following [Production method A], [Production method B] or [Production method C]. In these production methods, a protective group may be utilized for protecting a functional group from chemical reaction, if necessary.

[0012] [Production Method A]

[0013] Production method of making the compound given by formula [II] to react with the compound given by formula [III]

[0014] In the above scheme, L¹ represents a leaving group such as chlorine, bromine, iodine, p-toluenesulfonyloxy, methanesulfonyloxy and trifluoromethanesulfonyl; R¹¹ represents C1-C10 haloalkyl group such as fluoromethyl, difluoromethyl, bromodifluoromethyl and fluoroethoxy, C3-C10 haloalkenyl group such as 3,3-dichloroally or C3-C10 haloalkynyl group such as 2-propynyl; and R², X, Y, Ar, A, Z¹ and Z² have the same meanings as defined above.

[0015] Step 1 (process 1) in the above scheme is a process for producing the present compound given by formula [I-1] by making the compound given by formula [II] react with the compound given by formula [III] optionally in the presence of a base. The reaction temperature is usually in the range of 0-100° C. and the reaction period is usually in the range of 1-24 hours. The amount of the compound given by formula [III] utilized for the reaction is usually 0.5-10 mols, preferably 1-3 mols based on 1 mol of the compound given by formula [II].

[0016] When the base is utilized for the reaction, the amount of the base is usually 1-10 mols moles based on 1 mol of the compound given by formula [II]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride and the like; organic bases such as pyridine, triethylamine, ethyldiisopropylamine and the like; and mixtures thereof.

[0017] The reaction is usually carried out in a solvent. Examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitrites such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0018] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0019] The compound given by formula [I] wherein R¹ is trifluoromethyl can be prepared according to the methods described in Tetrahydron Lett., 1973, 2253 and J. Org. Chem., 1979, 44, 3872. At that time, Production Example 15 given below can be comferred.

[0020] The compound given by formula [II] wherein X is oxygen and Y is also oxygen (the compound given by formula [II-1] in the scheme below) can be prepared according to the methods described in Chem. Ber., 1971, 104, 2709, J. Org. Chem., 1966, 61, 3358 and Adv. Heterocycl. Chem., 1981, 31, 207. It can be concretely produced according to the following scheme.

[0021] In the above scheme, L³ and L⁴ are the same or different and represent alkoxy group such as t-butoxy group; L² represents chlorine or bromine atom; and R², Ar A, Z¹ and Z² have the same meanings as defined above.

[0022] The step 2-1 is a step of making the compound given by formula [IV] react with the compound given by formula [V] in the presence of a base to provide the compound given by formula [VI]. The reaction temperature is usually in the range of 0 to 100° C. and the amount of the compound given by formula [V] is usually 1 to 5 mols based on 1 mol of the compound given by formula [IV].

[0023] The amount of the base used for the reaction is usually 1 to 10 mols based on 1 mol of the compound given by formula [IV]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium hydride; organic bases such as pyridine, triethylamine and ethyldiisopropylamine; and mixtures thereof.

[0024] The reaction is usually carried out in a solvent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitrites such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0025] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0026] The step 2-2 is a step of making the compound given by formula [VI] react with the compound given by formula [VII-1] or formula [VII-2] to provide the compound given by formula [VIII]. The reaction temperature is usually in the range of 50 to 150° C., the reaction period is usually in the range of 1 to 24 hours and the amount of the compound given by formula [VII-1] or formula [VII-2] is usually 1 to 10 mols based on 1 mol of the compound given by formula [VI].

[0027] The reaction is usually carried out in a solvent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; nitrites such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

[0028] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0029] The step 2-3 is a step of making the compound given by formula [VIII] react with excess water in the presence of an acid to provide the compound given by formula [II-1]. The reaction temperature is usually in the range of 0 to 100° C. and examples of the acid include hydrochloric acid, sulfuric acid and p-toluenesulfonic acid. The amount of the acid is usually 0.1 to 100 mols based on 1 mol of the compound given by formula [VIII].

[0030] The reaction can be carried out in a solvent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

[0031] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0032] [Production method B]

[0033] Production method of making the compound given by formula [I-1] to react with 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (hereinafter, referred to as Lawesson's Reagent)

[0034] In the above scheme, R¹, R², X, Ar, A, Z¹ and Z² have the same meanings as defined above.

[0035] The step 3 is a step of making the compound given by formula [I-1] react with Lawesson's Reagent in a solvent to provide the compound given by formula [I-2]. The reaction temperature is usually in the range of 50 to 150° C. and the amount of the Lawesson's Reagent is usually 1 to 10 mols based on 1 mol of the compound given by formula [I-1].

[0036] Examples of the solvent used for the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

[0037] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0038] [Production method C]

[0039] Production method of making the compound given by formula [IX] to react with the compound given by formula [X]

[0040] In the above scheme, L⁵ represents p-toluenesulfonyl, methanesulfonyl or trifluoromethanesulfonyl, and R¹, R², Y, Ar, A, Z¹ and Z² have the same meanings as defined above.

[0041] The step 4 is a step of making the compound given by formula [IX] react with the compound given by formula [X]optionally in the presence of a base to provide the present compound given by formula [I]. The reaction temperature is usually in the range of 0 to 100° C., the reaction period is usually in the range of 1 to 24 hours and the amount of the compound given by formula [X] is usually 0.5 to 10 mols, preferably 1 to 3 mols based on 1 mol of the compound given by formula [IX].

[0042] When the base is utilized in the above reaction, the amount of the base is usually 1 to 10 mols based on 1 mol of the compound given by formula [X]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium hydride; organic bases such as pyridine, triethylamine and ethyldiisopropylamine; and mixtures thereof.

[0043] The reaction is usually carried out in a solent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0044] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0045] The compound given by formula [IX] can be, for example, produced according to the following scheme.

[0046] In the above scheme, L⁵, R², Ar, A, Z¹ and Z² have the same meanings as defined above.

[0047] The step 5 is a step of making the compound given by formula [II-1] react with the compound given by formula [X]optionally in the presence of a base to provide the present compound given by formula [IX]. The reaction temperature is usually in the range of −20 to 100° C., the reaction period is usually in the range of 1 to 24 hours and the amount of the compound given by formula [XI] is usually 0.5 to 10 mols, preferably 1 to 3 mols based on 1 mol of the compound given by formula [IX].

[0048] When the base is utilized in the above reaction, the amount of the base is usually 1 to 10 mols based on 1 mol of the compound given by formula [II-1]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium hydride; organic bases such as pyridine, triethylamine and ethyldiisopropylamine; and mixtures thereof.

[0049] The reaction is usually carried out in a solent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0050] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0051] The compound given by formula [IV] can be, for example, produced according to the following scheme.

[0052] wherein L² and Ar mean as described above.

[0053] The compound given by formula [XII] can be produced according to the description in Syn. Commun., 1982, 21, 415, JP sho58-41862A, Tetrahedron Lett., 1980,21,2547, Syn. Commun., 1976, 6, 349 and J. Am. Chem. Soc., 1977, 99, 4833.

[0054] The compound given by formula [V] can be produced according to the description in Bull. Chem. Soc, Jpn., 1990, 63, 1252, J. Am. Chem. Soc., 1955, 77, 2544, Synthesis, 1975, 590 and Chem. Lett., 1984, 1733.

[0055] When the present compound is used as an active ingredient of fungicide, it can be used as it is without any other ingredient, but it is usually formulated to emulsifiable concentrates, wettable powders, water dispersible granules, emulsion formulations, flowables, dusts, granules and so on by mixing with solid carrier, liquid carrier, surfactant or the other auxiliaries and used. These formulations usually contain 0.1 to 90% by weight of the present compound.

[0056] Examples of the solid carrier utilized for the formulation include fine powders or granules of minerals such as kaolin clay, attapulgite clay, bentonite, montmorillonite, terra alba, pyrophilite, talc, diatomaceous earth and calcite; natural organic substances such as corncob and walnut shell; synthetic organic substances such as urea; salts such as calcium carbonate and ammonium sulfate; and synthetic inorganic substances such as synthetic hydrous silicon oxide. Examples of the liquid carrier include aromatic hydrocarbons such as xylene, alkylbenzene and methylnaphthalene; alcohols such as isopropanol, ethylene glycol, propylene glycol and cellosolve; ketones such as acetone, cyclohexanone and isophorone; vegetable oils such as soybean oil and cottonseed oil; paraffin type aliphatic hydrocarbons; esters; dimethyl sulfoxide; acetonitrile and water.

[0057] Examples of the surfactant include anionic surfactants such as alkylsulfate ester salts, alkylarylsulfonate salts, dialkyl sulfosaccinate salts, polyoxyethylenealkylary ether phosphate salts, ligninsulfonate salts and naphthalenesulfonate formaldehyde condensate; nonionic surfactants such as polyoxyethylenealkylary ether, polyoxyethylenealkylpolyoxypropylene block copolymers and sorbitan fatty acid esters.

[0058] Examples of the auxiliaries for formulation include water soluble polymers such as polyvinyl alcohol and polyvinylpyrrolidone; polysaccharides such as gum arabic, algin acid and its salts, CMC(carboxymethylcellulose) and xanthan gum; inorganic substances such as alminium magnesium silicate and almina sol; preservatives; coloring agent; PAP (isopropyl acid phosphate) and stabilizers such as BHT.

[0059] The application methods of the present compounds are typically foliar application and soil treatment.

[0060] When the present compound is used for controlling plant diseases, the dosage is usually 1 to 5000 g, preferably 5 to 1000 g per 1 hectare though it is variable depending on the type of plants (e.g. crops) to be treated, type of diseases to be controlled, degree of affection by the diseases, formulation type, application method, time of application, weather conditions and so on.

[0061] In case emulsifiable concentrates, wettable powders, flowables and the like are used as aqueous dilution, the concentration of the active ingredient is 0.0001 to 3% by weight, preferably 0.0005 to 1% by weight. Dusts, granules and the like are applied as they are without dilution. The present compound is also used for the other known application methods such as seed treatment. When it is used for seed treatment, seeds are usually soaked in 1 to 1000 ppm dilution of the present compound, or said dilution is sprayed to or daubed on the seeds. Further, dusts containing 0.1 to 10% by weight of the present compound may be applied by powder treatment.

[0062] The present compound can be used as agricultural/horticultural fungicide for controlling plant diseases in the plowed fields, paddy fields, orchards, tea plantations, pastures, lawns and the like. Also, an increased fungicidal effect can be expected by using the compounds in admixture with other fungicides. Examples of such admixable other fungicide include azole type fungicidal compounds such as propiconazole, triadimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromconazole, epoxyconazole, diphenoconazole, ciproconazole, metoconazole, triflumizole, tetraconazole, microbutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, bitertanol, imazalil and flutriafol; cyclic amine type fungicidal compounds such as fenpropimorph, tridemorph and fenpropidin; benzimidazole type fungicidal compounds such as carbendazim, benomyl, thiabendazole and thiophanate-methyl; procymidone; cyprodinil; pyrimethanil; diethofencarb; thiuram; fluazinam; mancozeb; iprodione; vinclozolin; chlorothalonil; captan; mepanipyrim; fenpiclonil; fludioxonil; dichlofluanide; folpet; kresoxim-methyl; azoxystrobin; trifloxystrobin; picoxystrobin; pyraclostrobin; N-methyl- α-ethoxyimino-2-[(2,5-dimethylphenoxy) methyl]phenylactamide, spiroxamine; quinoxyfen; phenhexamid; famoxadone; fenamidon (RP-407213) and iprovalicarb.

[0063] The present compound can be used in combination with other agricultural/horticultural insecticides, acaricides, nematocides, herbicides, plant growth regulators and fertilizers. In the combination, they can be mixed in advance.

[0064] Examples of the insecticide, acaricide and nematocide include organophosphorus compounds such as fenitrothion [O,O-dimethyl O-(3-methyl-4 -nitrophenyl) phosphorothioate], fenthion [O,O-dimethyl O-(3-methyl-4-(methythio) phenyl) phosphorothioate], diazinon [O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4 -yl phosphorothioate], chlorpyrifos [O,O-diethyl O-3,5,6-trichloro-2 -pyridyl phosphorothioate], acephate [O,S-dimethyl acetylphosphoramidothioate], methidathion [S-2,3-dihydro-5-methoxy- 2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate], disulfoton [O,O-diethyl S-2-ethylthioethyl phosphorodithioate], DDVP [2,2-dichlorovinyl dimethyl phosphate], sulprofos [O-ethyl O-4-(methylthio)phenyl S-propyl phosphorodithioate], cyanophos [O-4-cyanophenyl O,O-dimethyl phosphorothioate], dioxabenzofos [2-methoxy-4H-1,3,2-benzodioxaphosphorin 2-sulfide], dimethoate [O,O-dimethyl S-(N-methylcarbamoylmethyl) dithiophosphate], phenthoate [ethyl 2-dimethoxyphosphinothioylthio(phenyl) acetate], malathion [diethyl (dimethoxyphosphinothioylthio) succinate], trichlorfon [dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate], azinphosmethyl [S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl O,O-dimethyl phosphorodithioate], monocrotophos [dimethyl (E)-1-methyl-2-(methylcarbamoyl) vinyl phosphate], ethion [O,O,O′,O′-tetraethyl S,S′-methylene bis (phosphorodithioate)] and fosthiazate [N-(O-methyl-S-sec-butyl) phosphorylthiazolidin-2-one]; carbamate compounds such as BPMC [2-sec-butylphenyl methylcarbamate], benfracarb [ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7 -yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate], propoxur [2- isopropoxyphenyl N-methylcarbamate], carbosulfan [2,3-dihydro-2,2-dimethyl-7 -benzo [b]furanyl N-dibuthylaminothio-N-methylcarbamate], carbaryl [1-naphthyl N-methylcarbamate], methomyl [S-methyl N-[(methylcarbamoyl)oxy]thioacetimidate], ethiofencarb [2-(ethylthiomethyl) phenyl methylcarbamate], aldicarb [2-methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime], oxamyl [N,N-dimethyl-2-methylcarbamoyloxyimino-2 -(methylthio)acetamide] and fenothiocarb [S-4-phenoxybuthyl N,N-dimethylthiocarbamate]; pyrethroid compounds such as etofenprox [2-(4-ethoxyphenyl)-2 -methylpropyl 3-phenoxybenzyl ether], fenvalerate [(RS)-α-cyano-3 -phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate], esfenvalerate [(S)-α-cyano-3-phenoxybenzyl (S) -2-(4-chlorophenyl)-3-methylbutyrate], fenpropathrin [(RS)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate], cypermethrin [(RS)-α-cyano-3-phenoxybenzyl (1RS, 3RS) -3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylate], permethrin [3-phenoxybenzyl (1RS,3RS)-3-(2,2-dichlorovinyl)-2, 2-dimethylcyclopropanecarboxylate], cyhalothrin [(RS)-α-cyano-3 -phenoxybenzyl (Z)-(1RS,3RS)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate), deltamethrin [(S)-α-cyano-m-phenoxybenzyl (1R, 3R) -3-(2,2-dibromovinyl)-2,2-dimethyl-cyclopropanecarboxylate], cycloprothrin [(RS)-α-cyano-3-phenoxybenzyl (RS)-2,2-dichloro-1-(4-ethoxyphenyl) cyclopropanecarboxylate], fluvalinate [α-cyano-3-phenoxybenzyl N-(2-chloro-α,α,α-trifluoro-p-tolyl)-D-valinate], bifenthrin [2-methylbiphenyl-3 -ylmethyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropanecarboxylate], acrinathrin [cyano(3-phenoxyphenyl)methyl (1R-{1α(S*), 3α(Z)})-2,2-dimethyl-3-[3-oxo-3-(2,2,2-trifluoro-1-(trifluoromethyl)ethoxy-1-propenyl) cycloprop anecarboxylate], 2-methyl-2-(4-bromodifluoromethoxyphenyl) propyl 3-phenoxybenzyl ether, tralomethrin [(S)-α-cyano-3-phenoxybenzyl (1R-cis) 3-(1,2,2,2-tetrabromoethyl)-2,2-dimethylcyclopropanecarboxylate], silafluofen [(4-ethoxyphenyl)(3-(4-fluoro-3-phenoxyphenyl)propyl) dimethylsilane]; thiadiazine derivatives such as buprofezin (2-t-butylimino-3-isopropyl-5-phenyl-1, 3,5-thiadiazin-4-one); nitroimidazolidine derivatives; nereistoxin derivatives such as cartap (S,S′-(2-dimethylaminotrimethylene)bis(thiocarbamate), thiocyclam [N,N′-dimethyl-1,2,3-trithian-5-ylamine] and bensultap [S,S′-2-dimethylaminotrimethylene di(benzenethiosulfonate)]; N-cyanoamidine derivatives such as N-cyano-N′-methyl-N′-(6-chloro-3-pyridylmethyl)acetamidine; chlorinated hydrocarbons such as endosulfan [6,7,8,9,10,10-hexachloro-1, 5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine oxide], γ-BHC [1,2,3,4,5,6-hexachlorocyclohexane] and 1,1-bis(chlorophenyl)-2,2,2-trichloroethanol; benzoylphenylurea compounds such as chlorfluazuron [1-(3,5-dichloro-4-(3-chloro-5-trifluoromethylpyridyn-2-yloxy)phenyl)-3 -(2,6-difluorobenzoyl)urea], teflubenzuron [1-(3,5-dichloro-2,4-difluorophenyl)-3 -(2,6-difluorobenzoyl)urea] and flufenoxuron [1-(4-(2-chloro-4 -trifluoromethylphenoxy)-2-fluorophenyl)-3-(2,6-difluorobenzoyl)urea]; formamidine derivatives such as amitraz [N,N′-[(methylimino)dimethylidine]di-2,4-xylidine] and chlordimeform [N′-(4-chloro-2-methylphenyl)-N,N-dimethylmethanimidamide]; thiourea derivatives such as diafenthiuron [N-(2,6-diisopropyl-4- phenoxyphenyl)-N′-t-butylcarbodiimide]; phenylpyrazole compounds; tebufenozide [N-t-butyl-N′-(4-ethylbenzoyl)-3,5-dimethylbenzhydrazide]; 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethylpyrrole-3-carbonitrile; bromopropylate [isopropyl 4,4′-dibromobenzilate]; tetradifon [4-chlorophenyl 2,4,5-trichlorophenyl sulfone]; quinomethionate [S,S-6-methylquinoxalin-2,3-diyl dithiocarbonate]; propargite [2-(4-t-butylphenoxy)cyclohexyl prop-2-yl sulfite]; fenbutatin oxide [bis[tris (2-methyl-2-phenylpropyl)tin]oxide]; hexythiazox [(4RS, 5RS)-5-(4-chlorophenyl)-N-chlorohexyl-4-methyl-2-oxo-1,3-thiazolidin-3-carboxamide]; clofentezine [3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine]; pyridathioben [2-t-butyl-5-(4-t-butylbenzylthio)-4-chloropyridazin-3(2H)-one]; fenpyroximate [t-butyl (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)methyleneaminooxymethyl]benzoate]; tebufenpyrad [N-(4-t-butylbenzyl)-4-chloro-3-ethyl-1-methyl-5-pyrazolecarboxamide]; polynactins complex [tetranactin, dinactin and trinactin]; milbemectin; abamectin; ivermectin; azadirachtin [AZAD]; pyrimidifen [5-chloro-N-[2-{4-(2-ethoxyethyl)-2,3-dimethylphenoxy}ethyl]-6-ethylpyrimidin-4-amine] and pymetrozine [2,3,4,5-tetrahydro-3-oxo-4-[(pyridin-3-yl)methyleneamino]-6-methyl-1,2,4-triazine.

[0065] Examples of the plant diseases to be controlled by the present compound include Pyricularia oryzae and Cochlioholus miyaheanus and Rhizoctonia solani of rice; Erysiphe graminis, Gibberella zeae, Puccinia striiformis, P. graminis, P. recondita, P. hordei, Typhula sp., Micronectriella nivalis, Ustilago tritici, U. nuda, Tilletia caries, Pseudocercosporella herpotrichoides, Rhynchosporium secalis, Septoria tritici and Leptosphaeria nodorum, of wheat and barley; Diaporthe citri, Elsinoe fawcetti, Penicillium digitatum and P. italicum of citrus; Sclerotinia mali, Valsa mali, Podosphaera leucotricha, Alternaria mali and Venturia inaequalis of apple; Venturia nashicola, V. pirina, Alternaria kikuchiana and Gymnosporangium haraeanum of pear; Sclerotinia cinerea, Cladosporium carpophilum and Phomopsis sp. of peach; Elsinoe ampelina, Glomerella cingulata, Uncinula necator, Phakopsora ampelopsidis, Guignardia bidwellii and Plasmopara viticola, of grape; Gloeosporium kaki, Cercospora kaki and Mycosphaerella nawae of Japanese persimmon; Colletotrichum lagenarium, Sphaerothecafuliginea, Mycosphaerella melonis, Fusarium oxysporum, Pseudoperonospora cubensis and Phytophthora sp. of gourd; Alternaria solani, Cladosporium fulvum, Phytophthora infestans and Pythium sp. of tomato; Phomopsis vexans and Erysiphe cichoracearum, of eggplant; Alternaria japonica and Cercosporella brassicae of Cruciferae vegetables; Puccinia allii of leek; Cercospora kikuchii, Elsinoe glycines and Diaporthe phaseolorum var. sojae of soybean; Colletotrichum lindemthianum of kidney bean; Cercospora personata and Cercospora arachidicola of peanut; Erysiphe pisi of pea; Alternaria solani and Phytophthora infestans of potato; Sphaerotheca humuli of strawberry; Exobasidium reticulatum and Elsinoe leucospila of tea; Alternaria longipes, Erysiphe cichoracearum, Colletotrichum tabacum, Peronospora tabacina and Phytophthora nicotianae of tobacco; Cercospora beticola of sugar beet; Diplocarpon rosae and Sphaerotheca pannosa of rose; Septoria chrysanthemi-indici and Puccinia horiana of chrysanthemum; and Botrytis cinerea and Sclerotinia sclerotiorum of various crops.

EXAMPLES

[0066] The present invention is explained by production examples, formulation examples and test examples below and it is not restricted by the following examples.

[0067] At first, the production examples of the present compounds and reference production examples of the intermediates of the present compounds. The numbers of the present compounds are the compound numbers described in the table below.

Production Example 1

[0068] Two hundred milligrams (200 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (0.586 mmol), 28 mg (0.70 mmol) of 60% sodium hydride, 2 ml of anhydrous N,N-dimethylformamide and 1 ml of anhydrous diethyl ether were mixed and 0.5 ml of bromofluoromethane was added thereto at −5° C. The mixture was stirred at −5° C. for 30 minutes and then stirred at 0° C. for 1 hour. The reaction mixture was added to water and extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate=2:1) to give 205 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1-4).

[0069]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(5H,m), 6.7-6.8(3H,m), 6.5(1H,s), 5.43(2H,d,J=53Hz), 3.87(3H,s), 3.85(3H,s), 3.62(2H,m), 2.84(2H,t), 2.34(3H,s)

[0070] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(3-methylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl) acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(3-methylphenyl)acrylamide (the present compound 1034) was obtained according to production example 1.

[0071]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.3(4H,m), 6.6-6.8(4H,m), 6.46(1H,br), 5.44(2H,d,J=53.4Hz), 3.86(3H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9Hz), 2.33(3H,s)

Production Example 2

[0072] Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (1.46 mmol), 0.31 g (1.7 mmol) of 30% aqueous potassium hydroxide solution, 0.1 g (0.3 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a small amount of 30% aqueous potassium hydroxide solution was further added, a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis. Then, 5% hydrochrolic acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to give 474 mg of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1005).

[0073]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.11-7.19(4H,m), 6.85(1H,s), 6.72-6.78 (3H,m), 6.36(1H,t,J=71.8Hz), 3.86(3H,s), 3.83(3H,s), 3.49(2H,m), 2.83(2H,t), 2.34(3H,s)

Production Example 3

[0074] One gram (1.00 g) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl) acrylamide (2.66 mmol), 130 mg (3.25 mmol) of 60% sodium hydride and 10 ml of anhydrous N,N-dimethylformamide were mixed and 0.46 g of bromofluoromethane was added thereto at −15° C. The mixture was stirred at −15° C. for 30 minutes and then stirred at 0° C. for 1 hour. The reaction mixture was added to water and extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate=1:1) to give 100 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(4-chlorophenyl)acrylamide (the present compound 1016).

[0075]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.3(4H,m), 6.5-6.8(5H,m), 5.41(2H,d, J=53.4Hz), 3.84(3H,s), 3.83(3H,s), 3.5-3.7(2H,m), 2.82(2H,t,J=6.9Hz)

Production Example 4

[0076] Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide (1.33 mmol), 2.00 g (3.56 mmol) of 10% aqueous potassium hydroxide solution, 87 mg (0.266 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis, 5% hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) and the obtained residue was washed with hexane to give 360 mg of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide.

[0077]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.4(4H,m), 6.7-6.9(4H,m), 6.35(1H,t, J=71.4Hz), 6.13(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.84(2H,t, J=6.8Hz)

Production Example 5

[0078] Five hundred miligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (1.47 mmol), 0.11 g (1.47 mmol) of 3-chloropropyne and 5 ml of anhydrous N,N-dimethylformamide were mixed and 64 mg (1.61 mmol) of 60% sodium hydride was added thereto at 0-5° C. The mixture was stirred at 0-10° C. for 30 minutes and then stirred at room temperature. Water was added to the reaction mixture, followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=1:1) to give 180 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(4-methylphenyl)acrylamide (the present compound 1182).

[0079]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.3(4H,m), 6.7-6.9(4H,m), 6.70(1H,s), 4.51(2H,d,J=2.4Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.59(1H,t, J=2.4Hz), 2.32(3H,s)

[0080] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl) acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(4-chlorophenyl)acrylamide (the present compound 1185) was obtained according to production example 5.

[0081]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.60(1H,s), 7.2-7.4(4H,m), 7.0-7.1(2H,m), 6.73(1H,d,J=7.9Hz), 6.62(1H,d,J=1.9Hz), 6.56(1H,dd,J=8.0,1.9Hz), 5.28(1H,br), 4.52(2H,d,J=2.3Hz), 3.87(3H,s), 3.83(3H,s), 3.4-3.6(2H,m), 2.71(2H,t,J=6.9Hz), 2.57(1H,t,J=2.2Hz)

Production Example 6

[0082] 0.76 g (2.0 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide and 8ml of anhydrous N,N-dimethylformamide were mixed and 0.5 ml of bromofluoromethane was added thereto at −15° C. 88 mg (2.2 mmol) of 60% sodium hydride was added and stirred at −15° C. for 30 minutes and then stirred at approximately 0° C. for 1.5 hours. Water was added to the reaction mixture, followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate=1:1) to give 0.68 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1103).

[0083]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.42(1H,br), 5.43(2H,d,J=53.7Hz), 3.85(3H,s), 3.84(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.7-2.8(4H,m), 1.7-1.9(4H,m)

Production Example 7

[0084] A mixture of 380 mg (0.920 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 420 mg (1.01 mmol) of Lawesson's Reagent and 5 ml of anhydrous tetrahydrofuran was refluxed by heating for 3 hours. Water and ethyl acetate were added to the reaction mixture, and the ethyl acetate layer was washed with aqueous sodium hydroxide solution, aqueous ammonium chloride solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 222 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylthioamide (the present compound 1160).

[0085]¹H-NMR(CDCl₃, TMS) δ(ppm): 8.11(1H,s), 7.0-7.1(2H,m), 6.77(2H,d, J=6.0Hz), 6.70(1H,d,J=8.2Hz), 6.60(1H,d,J=1.7Hz), 6.55(1H,dd,J=7.9,1.9Hz), 5.48(2H,d,J=53.5Hz), 3.9-4.0(2H,m), 3.85(3H,s), 3.81(3H,s), 2.83(2H,t,J=6.7Hz), 2.6-2.8(4H,m), 1.7-1.9(4H,m)

[0086] By using 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl)acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl) acrylthioamide (the present compound 1445) was obtained according to production example 7.

[0087]¹H-NMR(CDCl₃, TMS) δ(ppm): 8.20(1H,s), 7.1-7.2(2H,m), 6.8-7.0(4H,m), 6.38(1H,t, J=71.0Hz), 6.5-6.6(1H,m), 4.74(2H,s), 3.9-4.0(2H,m), 3.79(3H,s), 2.83(2H,t,J=6.8Hz), 2.52(1H,t,J=2.1Hz), 2.39(3H,s)

Production Example 8

[0088] Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (1.31 mmol), 1.80 g (3.28 mmol) of 10% aqueous potassium hydroxide solution, 87 mg (0.262 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. A sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis. Then, 5% hydrochrolic acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) and the obtained residue was washed with hexane to give 350 mg of 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1104).

[0089]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.1(3H,m), 6.7-6.9(4H,m), 6.36(1H,t, J=71.8Hz), 6.01(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.83(2H,t, J=6.9Hz), 2.6-2.8(4H,m), 1.7-1.9(4H,m)

[0090] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methoxyphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2- (5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methoxyphenyl)acrylamide (the present compound 1023) was obtained according to production example 8.

[0091]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.3(2H,m), 6.7-6.9(6H,m), 6.35(1H,t, J=71.7Hz), 6.04(1H,br), 3.86(3H,s), 3.82(3H,s), 3.80(3H,s), 3.6-3.7(2H,m), 2.83 (2H,t,J=6.8Hz)

[0092] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(naphthalen-2-yl)acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(naphthalen-2-yl)acrylamide (the present compound 2077) was obtained according to production example 8.

[0093]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.7-7.9(4H,m), 7.4-7.6(3H,m), 7.01(1H,s), 6.7-6.8(3H,m), 6.41(1H,t,J=71.6Hz), 6.08(1H,br), 3.84(3H,s), 3.79(3H,s), 3.6-3.7 (2H,m), 2.86(2H,t,J=6.9Hz)

[0094] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-bromophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 2-(4-bromophenyl)-3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]acrylamide (the present compound 1020) was obtained according to production example 8.

[0095]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.4-7.5(2H,m), 7.1-7.2(2H,m), 6.89(1H,s), 6.7-6.9(3H,m), 6.35(1H,t,J=71.4Hz), 6.14(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7 (2H,m), 2.84(2H,t,J=6.9Hz)

[0096] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-trifluoromethylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-trifluoromethylphenyl) acrylamide (the present compound 1029) was obtained according to production example 8.

[0097]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.4-7.6(4H,m), 6.95(1H,s), 6.7-6.9(3H,m), 6.37(1H,t,J=71.5Hz), 6.21(1H,br), 3.85(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.9Hz)

[0098] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(indan-5-yl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(indan-5-yl)acrylamide (the present compound 1122) was obtained according to production example 8.

[0099]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.2(3H,m), 6.6-6.9(4H,m), 6.35(1H,t, 71.7Hz), 6.02(1H,br), 3.85(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.8-3.0(6H,m), 2.0-2.1(2H,m)

[0100] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2- (4-nitrophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(4-nitrophenyl)acrylamide (the present compound 1247) was obtained according to production example 8.

[0101]¹H-NMR(CDCl₃, TMS) δ(ppm): 8.1-8.2(2H,m), 7.4-7.5(2H,m), 7.03(1H,s), 6.6-6.9(3H,m), 6.37(1H,t,J=70.8Hz), 6.28(1H,br), 3.8-3.9(6H,m), 3.6-3.7(2H,m), 2.86(2H,t,J=6.7Hz)

[0102] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylthiophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylthiophenyl)acrylamide (the present compound 1026) was obtained according to production example 8.

[0103]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.20(4H,s), 6.7-6.9(4H,m), 6.36(1H,t, J=71.5Hz), 6.07(1H,br), 3.86(3H,s), 3.82(3H,s), 3.6-3.7(2H,m), 2.84(2H,t, J=6.9Hz), 2.49(3H,s)

[0104] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(3,4-dichlorophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 2-(3,4-dichlorophenyl)-3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]acrylamide (the present compound 1065) was obtained according to production example 8.

[0105]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.3-7.5(2H,m), 7.14(1H,dd,J=8.5,2.1Hz), 6.90(1H,s), 6.7-6.9(3H,m), 6.35(1H,t,J=71.4Hz), 6.21(1H,br), 3.87(3H,s), 3.86(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz)

[0106] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-isopropylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-isopropylphenyl)acrylamide (the present compound 1251) was obtained according to production example 8.

[0107]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.2(4H,m), 6.7-6.9(4H,m), 6.38(1H,t, J=71.7Hz), 6.05(1H,br), 3.86(3H,s), 3.83(3H,s), 3.5-3.7(2H,m), 2.8-3.0(3H,m), 1.23(6H,d, J=6.8Hz)

[0108] By using N-[3-(3,4-dimethoxyphenyl)propyl]-3-hydroxy-2-(4-methylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[3-(3,4-dimethoxyphenyl)propyl]-2-(4-methylphenyl)acrylamide (the present compound 1476) was obtained according to production example 8.

[0109]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.3(4H,m), 6.87(1H,s), 6.7-6.8(3H,m), 6.46(1H,t,J=72.1Hz), 5.98(1H,br), 3.86(3H,s), 3.85(3H,s), 3.4-3.5(2H,m), 2.63(2H,t, J=7.43Hz), 2.34(3H,s), 1.8-2.0(2H,m)

Production Example 9

[0110] Five hundred milligrams (500 mg) of 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (1.16 mmol) and 5 ml of anhydrous N,N-dimethylformamide were mixed and cooled, and then 49 mg (1.22 mmol) of 60% sodium hydride was added thereto and stirred at 0° C. for 30 minutes. To the mixture, 164 mg (1.16 mmol) of methyl iodide was added and stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. Water was added to the reaction mixture, which which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate =3:1) to give 460 mg of 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1125).

[0111]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.5-7.1(7H,m), 6.38(1H,t,J=72.4Hz), 3.85 (3H,s), 3.82(3H,s), 3.7-3.8(2H,m), 2.8-3.0(5H,m), 2.6-2.8(4H,m), 1.7-1.9(4H,m)

Production example 10

[0112] Six hundred milligrams (600 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (1.57 mmol), 0.14 g (1.89 mmol) of 3-chloropropyne, 280 mg (2.05 mmol) of potassium carbonate and 10 ml of anhydrous N,N-dimethylformamide were mixed and stirred at room temperature. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =1:1) to give 415 mg of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-(2-propynyloxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1196).

[0113]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.69(1H,s), 4.50(2H,d,J=2.4Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 2.61(1H,t, J=2.4Hz), 1.7-1.9(4H,m)

[0114] By using 1,1,3-trichloropropene in place of 3-chloropropyne, 3-(3,3-dichloroallyloxy)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1232) was obtained according to production example 10.

[0115]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.0(3H,m), 6.7-6.9(4H,m), 6.53(1H,s), 5.98(1H,d,J=6.4Hz), 4.51(2H,d,J=6.5Hz), 3.86(3H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0116] By using 1-chloro-2-fluoroethane in place of 3-chloropropyne, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-(2-fluoroethoxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1241) was obtained according to production example 10.

[0117]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.99(3H,s), 6.93(1H,br), 6.7-6.9(3H,m), 6.60(1H,s), 4.4-4.7(2H,m), 4.0-4.2(2H,m), 3.86(6H,s), 3.6-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

Production Example 11

[0118] Three hundred milligrams (300 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (0.716 mmol), 20 mg (0.0766 mmol) of tetrabutylammonium fluoride, 100 mg (0.716 mmol) of potassium carbonate and 2 ml of carbon tetrachloride were mixed and stirred at room temperature. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =1:1) to give 140 mg of 3-(3-chloro-2-propynyloxy)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1223).

[0119]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.65(1H,s), 4.50(2H,d,J=2.6Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

Production Example 12

[0120] 239 mg of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (0.572 mmol), 128 mg (1.72 mmol) of 3-chloropropyne, 3 ml of anhydrous N,N-dimethylformamide and 20 mg (0.50 mmol) of 60% sodium hydride were mixed and stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 225 mg of 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1268).

[0121]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.69(1H,s), 4.50(2H,d, J=2.4Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 2.61(1H,t, J=2.4Hz), 1.7-1.9(4H,m)

[0122] By using bromoethane in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(4-ethoxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1143) was obtained according to production example 12.

[0123]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.99(3H,s), 6.7-6.9(4H,m), 6.37(1H,t,J=71.8Hz), 6.12(1H,br), 4.06(2H,q,J=8.1Hz), 3.80(3H,s), 3.5-3.7(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m), 1.44(3H,t,J=7.0Hz)

[0124] By using chloropropane in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(3-methoxy-4-propoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1258) was obtained according to production example 12.

[0125]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.1(3H,m), 6.4-6.9(4H,m), 6.36(1H,t, J=71.9Hz), 6.05(1H,br), 3.97(2H,t,J=6.8Hz), 3.82(3H,s), 3.5-3.7(2H,m), 2.6-2.9 (6H,m), 1.7-1.9(6H,m), 1.03(3H,t,J=7.4Hz)

[0126] By using chloroacetonitrile in place of 3-chloropropyne, N-[2-(4-cyanomethoxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1274) was obtained according to production example 12.

[0127]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.1(4H,m), 6.7-6.9(3H,m), 6.39(1H,t, J=71.8Hz), 6.10(1H,br), 4.79(2H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

[0128] By using allyl chloride in place of 3-chloropropyne, N-[2-(4-allyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1266) was obtained according to production example 12.

[0129]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.6-6.9(4H,m), 6.35(1H,t, J=71.9Hz), 5.9-6.2(2H,m), 5.2-5.5(2H,m), 4.58(2H,dd,J=3.9,1.3Hz), 3.83(3H,s), 3.5-3.7(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

[0130] By using 1-chloro-2-butyne in place of 3-chloropropyne, N-[2-{4-(2-butynyloxy)-3-methoxyphenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1269) was obtained according to production example 12.

[0131]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.9-7.0(1H,m), 6.84(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.7Hz), 6.03(1H,br), 4.69(2H,q,J=2.3Hz), 3.82(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.7-2.8(4H,m), 1.83(3H,t,J=2.2Hz), 1.7-1.8(4H,m)

[0132] By using methoxymethyl chloride in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(3-methoxy-4-methoxymethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1284) was obtained according to production example 12.

[0133]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.1(4H,m), 6.85(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.6Hz), 6.02(1H,br), 5.20(2H,s), 3.83(3H,s), 3.6-3.7(2H,m), 3.51(3H,s), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0134] By using isopropyl chloride in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(4-isopropoxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1259) was obtained according to production example 12.

[0135]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.6-6.9(4H,m), 6.35(1H,t, J=71.7Hz), 6.02(1H,br), 4.4-4.6(1H,m), 3.80(3H,s), 3.6-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m), 1.35(6H,d,J=6.1Hz)

Production Example 13

[0136] Eighty milligrams (80 mg) of acetyl chloride (1.00 mmol) were added to a mixture of 420 mg (1.00 mmol), of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, 120 mg (1.20 mmol) of triethylamine and 5 ml of tetrahydrofuran at 0° C. and stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. Water and ethyl acetate were added to the reaction mixture. The organic layer was washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =3:1) to give 260 mg of 3-difluoromethoxy-N-[2-(3-methoxy-4-acetyloxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1282).

[0137]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.01(3H,s), 6.7-7.0(4H,m), 6.34(1H,t, J=71.2Hz), 6.18(1H,br), 3.77(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.7Hz), 2.7-2.8 (4H,m), 2.30(3H,s), 1.7-1.8(4H,m)

Production example 14

[0138] One and a half grams (1.5 g) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (4.39 mmol), 193 mg (4.83 mmol) of 60% sodium hydride, 10 ml of anhydrous dimethoxyethane and 10 ml of anhydrous diethyl ether were mixed, 0.8 ml of dibromodifluoromethane was added thereto at 0° C. and stirred at 0° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 1.0 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-bromodifluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1197).

[0139]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.8(4H,m), 6.4(1H,s), 3.86(3H,s), 3.83(3H,s), 3.66(2H,m), 2.84(2H,t), 2.35(3H,s)

Production Example 15

[0140] Five hundred hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-bromodifluoromethoxy-2-(4-methylphenyl)acrylamide (1.06 mmol), 0.5 ml of hydrogen fluoride-pyridine complex, 340 mg (1.57 mmol) of mercury oxide and 1 ml of isopropyl ether were mixed and stirred at room temperature for 2 hours. Aqueous sodium bicarbonate solution and celite were added to the reaction mixture and filtered. Water was added to the filtrate, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from t-butyl methyl ether and hexane to give 0.35 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-trifluoromethoxy-2-(4-methylphenyl) acrylamide (the present compound 1006).

[0141]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.8(3H,m), 6.71(1H,s), 6.1(1H,s), 3.84(3H,s), 3.82(3H,s), 3.62(2H,m), 2.89(2H,t), 2.32(3H,s)

Production Example 16

[0142] 4.20 g (9.19 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 14.3 g (23.0 mmol) of 10% aqueous potassium hydroxide solution, 0.60 g (1.84 mmol) of tetrabutylammonium bromide and 40 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatography, 5% hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) and the obtained product was washed with hexane to give 2.4 g of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1281).

[0143]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 6.9-7.1(3H,m), 6.6-6.9(4H, m), 6.26(1H,t,J=71.6Hz), 6.02(1H,br), 5.13(2H,s), 3.84(3H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0144] By using N-[2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide in place of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, 3-difluoromethoxy-N-[2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1450) was obtained according to production example 16.

[0145]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.01(3H,s), 6.85(1H,s), 6.6-6.8(3H,m), 6.41(1H, t,J=71.6Hz), 6.02(1H,br), 4.24(4H,s), 3.5-3.7(2H,m), 2.7-2.8(6H,m), 1.7-1.9(4H,m)

[0146] By using N-[2-(3-chloro-4-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide in place of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, N-[2-(3-chloro-4-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1447) was obtained according to production example 16.

[0147]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.2(4H,m), 6.8-6.9(3H,m), 6.40(1H,t, J=71.6Hz), 6.00(1H,br), 3.88(3H,s), 3.5-3.6(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0148] By using N-[2-(4-methoxy-3-methylphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide in place of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, 3-difluoromethoxy-N-[2-(4-methoxy-3-methylphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1448) was obtained according to production example 16.

[0149]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.0(4H,m), 6.7-6.9(3H,m), 6.34(1H,t, J=71.7Hz), 6.00(1H,br), 3.81(3H,s), 3.5-3.7(2H,m), 2.7-2.8(6H,m), 2.17(3H,s), 1.7-1.9(4H,m)

Production Example 17

[0150] 2.40 g (4.73 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 1.20 g (7.09 mmol) of 48% hydrobromic acid and 30 ml of acetic acid were mixed and stirred at 80° C. for 2 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 1.81 g of 3-difluoromethoxy-N- [2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1371).

[0151]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.1(3H,m), 6.84(1H,d,J=3.3Hz), 6.80(1H,s), 6.6-6.7(2H,m), 6.36(1H,t,J=71.8Hz), 6.12(1H,br), 5.78(1H,s), 3.82(3H,s), 3.5-3.7(2H,m), 2.4-2.8(6H,m), 1.7-1.9(4H,m)

Production Example 18

[0152] 417 mg (1.00 mmol) of 3-difluoromethoxy-N-[2-(3-hydroxy-4-methoxyphenyl) ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 5 ml of anhydrous N,N-dimethylformamide, 74 mg (1.00 mmol) of 3-chloropropyne and 50 mg (1.25 mmol) of 60% sodium hydride were mixed and stirred at room temperature for 3 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 162 mg of 3- difluoromethoxy-N-[2-{4-methoxy-3-(2-propynyloxy)phenyl}ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1299).

[0153]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.8-6.9(4H,m), 6.37(1H,t, J=71.7Hz), 6.03(1H,br), 4.71(2H,d,J=2.4Hz), 3.85(3H,s), 3.6-3.7(2H,m), 2.83(2H, t,J=6.8Hz), 2.7-2.8(4H,m), 2.47(1H,t,J=2.4Hz), 1.7-1.9(4H,m)

[0154] By using bromoethane in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(3-ethoxy-4-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1320) was obtained according to production example 18.

[0155]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.36(1H,t, J=71.7Hz), 6.02(1H,br), 4.04(2H,q,J=7.0Hz), 3.84(3H,s), 3.5-3.7(2H,m), 2.7-2.9 (6H,m), 1.7-1.9(4H,m), 1.44(3H,t,J=7.0Hz)

[0156] By using chloroacetonitrile in place of 3-chloropropyne, N-[2-(3-cyanomethoxy-4-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1305) was obtained according to production example 18.

[0157]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.8-7.1(7H,m), 6.40(1H,t,J=72.1Hz), 6.05(1H,br), 4.77(2H,s), 3.86(3H,s), 3.5-3.7(2H,m), 2.84(2H,t,J=6.9Hz), 2.7-2.8(4H,m), 1.7-1.9(4H,m)

Production Example 19

[0158] Five hundred milligrams (500 mg) of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide (1.33 mmol), 5 ml of anhydrous N,N-dimethylformamide, 196 mg (2.65 mmol) of 3-chloropropyne and 60 mg (1.46 mmol) of 60% sodium hydride were stirred at room temperature for 2 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 242 mg of 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-2-(4-methylphenyl)acrylamide (the present compound 1353).

[0159]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.95(1H,d,J=8.25Hz), 6.85(1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.7Hz), 6.11(1H,br), 4.73(2H,d,J=2.3Hz), 3.81(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.49(1H,d,J=2.4Hz), 2.32(3H,s)

[0160] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(indan-5-yl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(indan-5-yl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1360) was obtained according to production example 19.

[0161]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.0(2H,m), 6.9-7.1(2H,m), 6.85(1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.6Hz), 6.06(1H,br), 4.74(2H,d,J=2.4Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.8-2.9(6H,m), 2.49(1H,t,J=2.4Hz), 2.0-2.2(2H,m)

[0162] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methoxyphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(4-methoxyphenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1358) was obtained according to production example 19.

[0163]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(2H,m), 6.7-7.0(6H,m), 6.34(1H,t,J=71.6Hz), 6.05(1H,br), 4.74(2H,d,J=2.5Hz), 3.83(3H,s), 3.81(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.8Hz), 2.49(1H,t,J=2.5Hz)

[0164] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-phenylacrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3- difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-phenylacrylamide (the present compound 1388) was obtained according to production example 19.

[0165]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.3-7.4(5H,m), 6.96(1H,d,J=8.7Hz), 6.90(1H,s), 6.7-6.8(2H,m), 6.36(1H,t,J=71.5Hz), 6.07(1H,br), 4.75(2H,d,J=2.4Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz), 2.50(1H,t,J=2.4Hz)

[0166] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-trifluoromethylphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-trifluoromethylphenyl)acrylamide (the present compound 1357) was obtained according to production example 19.

[0167]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.59(2H,d,J=8.2Hz), 7.43(2H,d,J=8.0Hz), 6.9-7.0(2H,m), 6.7-6.8(2H,m), 6.35(1H,t,J=71.0Hz), 6.21(1H,br), 4.75(2H,d, J=2.2Hz), 3.84(3H,s), 3.6-3.7(2H,m), 2.87(2H,t,J=6.8Hz), 2.49(1H,t,J=2.2Hz)

[0168] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-ethylphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(4-ethylphenyl)-N-[2-{3-methoxy-4- (2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1354) was obtained according to production example 19.

[0169]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.3(4H,m), 6.96(1H,d,J=8.7Hz), 6.87 (1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.6Hz), 6.06(1H,br), 4.75(2H,d,J=2.4Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz), 2.64(2H,q,J=6.8Hz), 2.50(1H,t, J=2.4Hz)

[0170] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-fluorophenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(4-fluorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1392) was obtained according to production example 19.

[0171]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(2H,m), 6.9-7.1(3H,m), 6.87(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.3Hz), 6.17(1H,br), 4.76(2H,d,J=2.4Hz), 3.85(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz), 2.64(2H,q,J=6.8Hz), 2.50(1H,t,J=2.4Hz)

[0172] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(naphthalen-2-yl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(naphthalen-2-yl)acrylamide (the present compound 2202) was obtained according to production example 19.

[0173]¹H- NMR(CDCl₃, TMS) δ(ppm): 7.7-7.9(4H,m), 7.4-7.5(3H,m), 7.02(1H,s), 6.93(1H,d,J=8.6Hz), 6.7-6.8(2H,m), 6.39(1H,t,J=71.5Hz), 6.11(1H,br), 4.72(2H,d, J=2.2Hz), 3.78(3H,s), 3.6-3.7(2H,m), 2.87(2H,t,J=6.8Hz), 2.48(1H,t,J=2.5Hz)

[0174] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5-methylthiophen-2-yl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(5-methylthiophen-2-yl)-N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]acrylamide (the present compound 2133) was obtained according to production example 19.

[0175]¹H-NMR(CDCl₃, TMS) δppm): 7.62(1H,s), 6.95(1H,d,J=8.6Hz), 6.15-6.72 (3H,m), 6.4(1H,br), 4.74(2H,d,J=2.4Hz), 3.83(3H,s), 3.6(2H,m), 2.79(2H,t, J=6.9Hz), 2.50(1H,t,J=2.4Hz), 2.47(3H,s)

[0176] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(3,4-dichlorophenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(3,4-dichlorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1429) was obtained according to production example 19.

[0177]¹H-NMR(CDCl₃, TMS) δppm): 7.4-7.5(2H,m), 7.13(1H,dd,J=2.14, 8.2Hz), 6.97(1H,d,J=7.1Hz), 6.92(1H,s), 6.7-6.8 (2H,m), 6.0-6.7(2H,m), 4.75(2H,d,J=2.4Hz), 3.84(3H,s), 3.6(2H,m), 2.85(2H,t, J=6.5Hz), 2.51(1H,t,J=2.4Hz)

[0178] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-N-[2-(3-methoxy-4-(2-propynyloxy)phenyl)-1-methylethyl]-2-(4-methylphenyl) acrylamide (the present compound 1465) was obtained according to production example 19.

[0179]¹H-NMR(CDCl₃, TMS) δppm): 7.1-7.2(4H,m), 6.95(1H,d,J=7.9Hz), 6.85(1H,s), 6.7-6.8 (2H,m), 6.36(1H,t,J=71.7Hz), 5.78(1H,d,J=7.8Hz), 4.75(2H,d,J=2.2Hz), 4.3-4.5(1H,m), 3.82(3H,s), 2.7-2.9(2H,m), 2.49(1H,t, J=2.1Hz), 2.34(3H,s), 1.20(3H,d,J=6.7Hz)

[0180] By using bromomethylcyclopropane in place of 3-chloropropyne, N-[2-(4-cyclopropylmethoxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl) acrylamide (the present compound 1271) was obtained according to production example 19.

[0181]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.9(4H,m), 6.35(1H,t, J=71.7Hz), 6.01(1H,br), 3.8-3.9(5H,m), 3.6-3.7(2H,m), 2.82(2H,t, J=6.8Hz), 2.33(3H,s), 1.2-1.4(1H,m), 0.6-0.7(2H,m), 0.3-0.4(2H,m)

Production Example 20

[0182] 477 mg (1.20 mmol) of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-chlorophenyl)acrylamide, 5 ml of anhydrous N,N-dimethylformamide, 180 mg (2.40 mmol) of 3-chloropropyne and 72 mg (1.80 mmol) of 60% sodium hydride were stirred at room temperature for 2 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 70 mg of 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-chlorophenyl) acrylamide (the present compound 1355).

[0183]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.4(4H,m), 6.97(1H,d,J=8.7Hz), 6.89 (1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.3Hz), 6.17(1H,br), 4.75(2H,d,J=2.4Hz), 3.84(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=7.0Hz), 2.50(1H,d,J=2.4Hz)

Production Example 21

[0184] Two hundred milligrams (200 mg) of 3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide (0.611 mmol), 2 ml of anhydrous N,N-dimethylformamide, 144 mg (1.22 mmol) of 3-bromopropyne and 173 mg (1.25 mmol) of potassium carbonate were stirred at room temperature for 2 hours and then at 50° C. for 4 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 100 mg of N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-3-(2-propynyloxy)-2-(4-methylphenyl)acrylamide (the present compound 1364).

[0185]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.98(1H,d,J=8.6Hz), 6.6-6.9(4H,m), 4.74(2H,d,J=2.5Hz), 4.49(2H,d,J=2.5Hz), 3.85(3H,s), 3.6-3.7 (2H,m), 2.83(2H,t,J=6.9Hz), 2.59(1H,d,J=2.3Hz), 2.50(1H,d,J=2.2Hz), 2.32(3H,s)

Production Example 22

[0186] Three hundred milligrams (300 mg) of 3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-chlorophenyl)acrylamide (0.863 mmol) and 3 ml of anhydrous N,N-dimethylformamide were mixed and 320 mg (4.32 mmol) of 3-chloropropyne was added thereto at 0-5° C., and then 100 mg (2.59 mmol) of 60% sodium hydride was added at 0-5° C. The mixture was stirred for 1 hour at 0-5° C. and further at room temperature. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) to give 160 mg of 2-(4-chlorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-(2-propynyloxy) acrylamide (the present compound 1367).

[0187]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(4H,m), 6.9-7.0(2H,m), 6.7-6.8 (3H,m), 4.75(2H,d,J=2.4Hz), 4.52(2H,d,J=2.4Hz), 3.86(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9Hz), 2.63(1H,d,J=2.4Hz), 2.51(1H,d,J=2.42Hz)

Production Example 23

[0188] 4.17 g (10.00 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide, 22.4 g (40.0 mmol) of 10% aqueous potassium hydroxide solution, 1.62 g (5.00 mmol) of tetrabutylammonium bromide and 50 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatography, 5% hydrochloric acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with diethyl ether to give 3.46 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1451).

[0189]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 7.1-7.2(4H,m), 6.84(1H,s), 6.80(1H,d,J=8.2Hz), 6.74(1H,d,J=1.6Hz), 6.65(1H,dd,J=8.0,1.8Hz), 6.26(1H,t, J=71.6Hz), 6.02(1H,br), 5.13(2H,s), 3.84(3H,s), 3.6-3.7(2H,m), 2.81(2H,t, J=6.8Hz), 2.33(3H,s)

Production Example 24

[0190] 9.40 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide (20.1 mmol), 3.72 g (22.1 mmol) of 48% hydrobromic acid and 95 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. The solvent was distilled off from the reaction mixture under reduced pressure and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 4.55 g of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide (the present compound 1452).

[0191]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.8-6.9(2H,m), 6.6-6.7(2H,m), 6.35(1H,t,J=71.7Hz), 6.02(1H,br), 5.51(1H,s), 3.84(3H,s), 3.6-3.7(2H,m), 2.81(2H,t, J=6.9Hz), 2.34(3H,s)

Production Example 25

[0192] 1.48 g (3.38 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide, 4.3 g (8.46 mmol) of 10% aqueous potassium hydroxide solution, 220 mg (0.677 mmol) of tetrabutylammonium bromide and 15 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatography, 5% hydrochloric acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to give 1.45 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)-3-difluoromethoxyacrylamide (the present compound 1453).

[0193]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(9H,m), 6.87(1H,s), 6.80(1H,d, J=8.3Hz), 6.75(1H,d,J=2.0Hz), 6.66(1H,dd,J=8.0,2.0Hz), 6.23(1H,t,J=71.7Hz), 6.12(1H,br), 5.14(2H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.82(2H,t,J=6.8Hz)

Production Example 26

[0194] 1.45 g (2.97 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)-3-difluoromethoxyacrylamide, 751 mg (4.46 mmol) of 48% hydrobromic acid and 15 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 880 mg of 2-(4-chlorophenyl)-3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acrylamide (the present compound 1454).

[0195]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.4(4H,m), 6.88(1H,s), 6.84(1H,d, J=7.8Hz), 6.6-6.8(2H,m), 6.34(1H,t,J=71.4Hz), 6.14(1H,br), 5.53(1H,s), 3.85 (3H,s), 3.6-3.7(2H,m), 2.82(2H,t,J=6.8Hz)

Reference Production Example 1

[0196] A mixture of 5.00 g (33.3 mmol) of (4-methylphenyl)acetic acid, 5.94 g (49.9 mmol) of thionyl chloride, 0.12 g (1.6 mmol) of N,N-dimethylformamide and 20 ml of toluene was stirred at 100° C. for 1 hour, cooled and concentrated under reduced pressure. The residue was added to a mixture of 6.34 g (35.0 mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 8.6 g (67 mmol) of diisopropylethylamine and 25 ml of toluene at 0° C. and kept at 0° C. for 30 minutes and at room temperature for 6 hours. Water and ethyl acetate were added to the reaction mixture and precipitated solid was collected with filtration. The obtained solid was dried to give 5.76 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide.

[0197]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.2(4H,m), 6.72(1H,d,J=8.2Hz), 6.57-6.60(2H, m), 5.4(1H,s), 3.86(3H,s), 3.82(3H,s), 3.49(2H,s), 3.43(2H,m), 2.67(2H,t,J=6.9Hz), 2.34(3H,s)

[0198] One gram (1.0 g) of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylphenyl) acetamide (3.2 mmol), 1.68 g (9.64 mmol) of t-butoxybis(dimethylamino)methane and 15 ml of N,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours and then at 110° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to give 1.20 g of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2- (4-methylphenyl)acrylamide.

[0199] One gram (1.0 g) of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-methylphenyl)acrylamide (2.7 mmol), 12 ml of 5% hydrochloric acid and 20 ml of tetrahydrofuran were mixed and stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 0.76 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

[0200]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.26(1H,s), 7.0-7.1(4H,m), 6.6-6.7(3H,m), 5.5(1H,s), 3.86(3H,s), 3.82(3H,s), 3.51(2H,m), 2.75(2H,t,J=6.9Hz), 2.35(3H,s)

Reference Production Example 2

[0201] A mixture of 5.00 g (29.3 mmol) of (4-chlorophenyl)acetic acid, 5.23 g (43.9 mmol) of thionyl chloride and 50 ml of toluene was stirred at 50° C. for 30 minutes and then 80° C. for 2.5 hours, cooled and concentrated under reduced pressure. The residue was added to a mixture of 5.18 g (28.5 mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 3.46 g (34.2 mmol) of triethylamine and 50 ml tetrahydrofuran at 0° C. and kept at 0° C. for 30 minutes and at room temperature for 3 hours. Water and ethyl acetate were added to the reaction mixture and precipitated solid was collected with filtration. The obtained solid was dried to give 5.75 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide.

[0202]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(2H,m), 7.0-7.1(2H,m), 6.72(1H,d, J=8.1Hz), 6.61(1H,d,J=2.0Hz), 6.51(1H,dd,J=8.0,1.9Hz), 5.31(1H,br), 3.87(3H,s), 3.83(3H,s), 3.4-3.5(4H,m), 2.68(2H,t,J=6.8Hz)

[0203] 5.75 g (17.2 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide, 9.00 g (51.6 mmol) of t-butoxybis(dimethylamino)methane and 90 ml of N,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours and then at 110° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to give 6.68 g of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-chlorophenyl)acrylamide.

[0204] 6.60 g (17.2 mmol) of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-chlorophenyl)acrylamide, 80 ml of 5% hydrochloric acid and 100 ml of tetrahydrofuran were mixed and stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 4.46 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide.

[0205]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.66(1H,d,J=11.34Hz), 7.2-7.3(2H,m), 7.0-7.1(3H,m), 6.74(1H,d,J=8.1Hz), 6.5-6.6(2H,m), 5.32(1H,br), 3.87(3H,s), 3.80(3H,s), 3.5-3.6(2H,m), 2.75(2H,d,J=6.8Hz)

Reference Production Example 3

[0206] According to the description of JP hei10-87602A, (5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid was obtained.

[0207] A mixture of 3.60 g (18.9 mmol) of (5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid, 3.38 g (28.4 mmol) of thionyl chloride and 40 ml of toluene was stirred at 50° C. for 30 minutes and then 80° C. for 2.5 hours, cooled and concentrated under reduced pressure. The residue was added to a mixture of 3.43 g (18.9 mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 2.30 g (22.7 mmol) of triethylamine and 40 ml of tetrahydrofuran at 0° C. and kept at 0° C. for 30 minutes and at room temperature for 3 hours. Water and ethyl acetate were added to the reaction mixture and precipitated solid was collected with filtration. The obtained solid was dried to give 5.78 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide.

[0208]¹H-NMR(CDCl₃, TMS) δ(ppm): 6.99(1H,d,J=8.1Hz), 6.8-6.9(2H,m), 6.5-6.8(3H,m), 5.42(1H,br), 3.85(3H,s), 3.82(3H,s), 3.4-3.5(4H,m), 2.6-2.8(6H,m), 1.7-1.9(4H,m)

[0209] 2.65 g (7.50 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide, 3.92 g (22.5 mmol) of t-butoxybis (dimethylamino)methane and 30 ml of N,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours and then at 110° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to give 3.30 g of crude N-[2-(3,4-dimethoxyphenyl) ethyl]-3-dimethylamino-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide.

[0210] Three grams (3.00 g) of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (7.35 mmol), 30 ml of 5% hydrochloric acid and 30 ml of tetrahydrofuran were mixed and stirred at room temperature for 1.5 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 2.20 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide.

[0211]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.61(1H,d,J=11.2Hz), 6.9-7.1(2H,m), 6.6-6.8(5H, m), 5.56(1H,br), 3.86(3H,s), 3.82(3H,s), 3.4-3.6(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

Reference Production Example 4

[0212] 15.2 g (0.1 mol) of vanilline, 20.5 g (0.12 mol) of benzyl bromide, 17.9 g (0.13 mol) of potassium carbonate and 150 ml of N,N-dimethylformamide were mixed and stirred at 50° C. for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and then saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 23.1 g of 4-benzyloxy-3-methoxybenzaldehyde.

[0213]¹H-NMR(CDCl₃, TMS) δ(ppm): 9.83(1H,s), 7.5-7.3(7H,m), 6.98(1H,d, J=8.2Hz), 5.24(2H,s), 3.95(3H,s)

[0214] 23.1 g (95.7 mmol) of 4-benzyloxy-3-methoxybenzaldehyde, 8.76 g (143 mmol) of nitromethane and 250 ml of acetic acid were mixed and 7.07 g (96.7 mmol) of butylamine was added dropwise thereto. The mixture was refluxed for 2 hours by heating, and then cooled and poured into ice-water. The precipitated crystals were dissolved with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 17.0 g of 1-benzyloxy-2-methoxy-4-(2-nitrovinyl)benzene.

[0215]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.95(1H,d,J=13.5Hz), 7.51(1H,d,J=14.7Hz), 7.3-7.5(5H,m), 5.24(2H,s), 3.95(3H,s)

[0216] 6.78 g (178.8 mmol) of lithium aluminum hydride and 200 ml of anhydrous tetrahydrofuran were mixed and an anhydrous tetrahydrofuran solution of 17.0 g (59.6 mmol) of 1-benzyloxy-2-methoxy-4-(2-nitrovinyl)benzene was added dropwise thereto over about 90 minutes under vigorous stirring. The mixture was refluxed for 2 hours by heating, and then cooled and aqueous sodium hydroxide solution was added to the mixture. The precipitates were filtered off with celite-precoated glass filter and the solvent was distilled off from the filtrate under reduced pressure. The residue was extracted with ethyl acetate, washed with saturated brine, dried over potassium carbonate and the solvent was distilled off under reduced pressure to give 13.67 g of crude 2-(3-methoxy-4-benzyloxyphenyl) ethylamine.

[0217]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 6.6-6.9(3H,m), 5.10(2H,s), 3.85(3H,s), 2.90(2H,t,J=6.7Hz), 2.66(2H,t,J=6.8Hz), 2.0-2.4(2H,br)

[0218] 8.01 g (31.2 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine, 3.78 g (37.4 mmol) of triethylamine and 80 ml of tetrahydrofuran were mixed and cooled to 0° C. and then (5,6,7,8-tetrahydronaphthalen-2-yl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and then saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 8.3 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2 -yl)acetamide.

[0219]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.72(1H,d,J=8.2Hz), 6.5-6.6(2H,m), 5.4(1H,s), 3.86(3H,s), 3.82(3H,s), 3.49(2H,s), 3.3-3.4(2H,m), 2.67(2H,t,J=6.9Hz), 2.34(3H,s)

[0220] 8.8 g (13.6 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide, 8.9 g (51.1 mmol) of t-butoxybis (dimethylamino)methane and 100 ml of N,N-dimethylformamide were mixed and stirred at 100° C. for 6 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. To the residue, 50 ml of 5% hydrochloric acid and 100 ml of tetrahydrofuran were added and stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) and dried to give 4.20 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide.

[0221]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.61(1H,d,J=11.3Hz), 7.2-7.5(5H,m), 7.04(1H,d, J=11.0Hz), 6.97(1H,d,J=8.2Hz), 6.7-6.9(3H,m), 6.66(1H,d,J=2.0Hz), 6.59(1H,dd,J=8.3, 1.9Hz), 5.55(1H,br), 5.11(2H,s), 3.83(3H,s), 3.4-3.6(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

Reference Production Example 5

[0222]15.26 g (59.3 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine, 9.09 g (89.0 mmol) of triethylamine and 100 ml of tetrahydrofuran were mixed and cooled to about 0° C. and then 5.44 g (32.28 mmol) of (4-methylphenyl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 19.48 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide.

[0223]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 7.0-7.1(4H,m), 6.73(1H,d, J=8.2Hz), 6.62(1H,d,J=1.9Hz), 6.46(1H,dd,J=8.1,1.9Hz), 5.34(1H,br), 5.12(2H,s), 3.83(3H,s), 3.4-3.5(4H,m), 2.64(2H,t,J=6.9Hz), 2.32(3H,s)

[0224] 11.68 g (30.0 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl) acetamide and 15.67 g (90.0 mmol) of t-butoxybis(dimethylamino) methane were mixed and stirred at 80° C. for 2 hours. The reaction mixture was cooled and tetrahydrofuran was added thereto. The reaction mixture was acidified with 5% hydrochloric acid and stirred at room temperature for 2 hours. After the solvent was distilled off under reduced pressure, water and 5% hydrochloric acid were added to the residue, which was followed by extracted with chloroform twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 11.30 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

[0225]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.61(1H,d,J=11.3Hz), 7.2-7.5(5H,m), 6.9-7.1(5H,m), 6.77(1H,d,J=8.1Hz), 6.64(1H,d,J=1.6Hz), 6.56(1H,dd,J=8.1,1.6Hz), 5.46(1H,br), 5.13(2H,s), 3.83(3H,s), 3.4-3.6(2H,m), 2.73(2H,t,J=6.8Hz), 2.33(3H,s)

Reference Production Example 6

[0226] 2.14 g (11.97 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine, 1.45 g (14.36 mmol) of triethylamine and 20 ml of tetrahydrofuran were mixed and cooled to about 0° C. and then 2.26 g (11.97 mmol) of (4-chlorophenyl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 3.70 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)acetamide.

[0227]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(7H,m), 7.0-7.1(2H,m), 6.73(1H,d, J=8.3Hz), 6.63(1H,d,J=2.0Hz), 6.43(1H,dd,J=8.0,2.0Hz), 5.29(1H,br), 5.14(2H,s), 3.84(3H,s), 3.4-3.5(4H,m), 2.66(2H,t,J=6.8Hz)

[0228] 2.25 g (5.49 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide and 2.39 g (13.73 mmol) of t-butoxybis(dimethylamino) methane were mixed and stirred at 90° C. for 1.5 hours. The reaction mixture was cooled and tetrahydrofuran was added thereto. The reaction mixture was acidified with 5% hydrochloric acid and stirred at room temperature for 2 hours. After the solvent was distilled off under reduced pressure, water and 5% hydrochloric acid were added to the residue, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 1.50 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide.

[0229]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.67(1H,d,J=11.0Hz), 7.2-7.5(7H,m), 6.9-7.1(3H,m), 6.76(1H,d,J=8.3Hz), 6.65(1H,d,J=1.8Hz), 6.52(1H,dd,J=8.0,2.0Hz), 5.32(1H,br), 5.15(2H,s), 3.84(3H,s), 3.4-3.6(2H,m), 2.73(2H,t,J=6.8Hz)

Reference Production Example 7

[0230] Two grams (2.00 g) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (4.79 mmol), 1.21 g (7.19 mmol) of 48% hydrobromic acid and 20 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. The solvent was distilled off from the reaction mixture under reduced pressure and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 630 mg of 3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide.

[0231]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.6(1H,d,J=11.3Hz), 6.9-7.2(5H,m), 6.80(1H,d, J=7.8Hz), 6.5-6.6(2H,m), 5.4-5.5(2H,m), 3.83(3H,s), 3.4-3.6(2H,m), 2.74(2H,t,J=6.9Hz), 2.35(3H,s)

Reference Production Example 8

[0232] 1.60 g (3.66 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide, 925 mg (5.49 mmol) of 48% hydrobromic acid and 15 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 600 mg of 2-(4-chlorophenyl)-3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]acrylamide.

[0233]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.6(1H,d,J=11.3Hz), 7.2-7.4(2H,m), 7.0-7.1(3H, m), 6.82(1H,d,J=6.7,1.7Hz), 6.5-6.6(2H,m), 5.54(1H,s), 5.32(1H,br), 3.83(3H,s), 3.4-3.6 (2H,m), 2.74(2H,t,J=6.9Hz)

Reference Production Example 9

[0234] 4.02 g (55.0 mmol) of butylamine was added dropwise to a mixture of 12.1 g (50.0 mmol) of 4-benzyloxy-3-methoxybenzaldehyde, 5.63 g (75.0 mmol) of nitroethane and 120 ml of acetic acid and refluxed for 5 hours by heating. The reaction mixture was cooled and extracted with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =4:1) to give 2.70 g of 1-benzyloxy-2-methoxy-4-(2-nitropropenyl)benzene.

[0235]¹H-NMR(CDCl₃, TMS) δ(ppm): 8.04(1H,s), 7.3-7.5(5H,m), 6.9-7.1(3H,m), 5.21(2H,s), 3.92(3H,s), 2.47(3H,s)

[0236] To a mixture of 1.03 g (27.1 mmol) of lithium aluminum hydride and 20 ml of anhydrous tetrahydrofuran, an anhydrous tetrahydrofuran solution of 2.70 g (9.03 mmol) of 1-benzyloxy-2-methoxy-4-(2-nitropropenyl)benzene was added dropwise under vigorous stirring over about 90 minutes and refluxed for 2 hours by heating. The reaction mixture was cooled and aqueous sodium hydroxide solution was added thereto. After the precipitates were filtered off with celite-precoated glass filter, the solvent was distilled off from the filtrate under reduced pressure. The residue was extracted with ethyl acetate, washed with saturated brine, dried over potassium carbonate and the solvent was distilled off under reduced pressure to give 2.30 g of crude 2-(4-benzyloxy-3-methoxyphenyl)-1-methylethylamine.

[0237]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 6.6-6.9(3H,m), 5.12(2H,s), 3.87 (3H,s), 3.1-3.2(1H,m), 2.4-2.8(2H,m), 1.4-2.0(2H,br), 1.11(3H,d,J=6.3Hz)

[0238] 2.30 g (8.48 mmol) of crude 2-(4-benzyloxy-3-methoxyphenyl)-1-methylethylamine, 1.03 g (10.2 mmol) of triethylamine and 25 ml of tetrahydrofuran were mixed and cooled to about 0° C. and then 1.42 g (8.48 mmol) of (4-methylphenyl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 2.40 g of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl) acetamide.

[0239]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.3-7.5(5H,m), 6.9-7.1(4H,m), 6.72(1H,d,J=8.1Hz), 6.62(1H,d,J=1.9Hz), 6.42(1H,dd,J=2.0,8.1Hz), 5.1-5.3(2H,m), 4.1-4.3(1H,m), 3.83(3H,s), 3.45(2H,s), 2.59(2H,d,J=6.4Hz), 2.33(3H,s), 1.04(3H,d,J=6.6Hz)

[0240] 2.40 g (5.95 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acetamide and 3.10 g (17.8 mmol) of t-butoxybis(dimethylamino) methane were mixed and stirred at 80° C. for 2 hours. The reaction mixture was cooled and tetrahydrofuran was added thereto. The reaction mixture was acidified with hydrochloric acid and stirred at room temperature for 2 hours. After the solvent was distilled off under reduced pressure, the residue was extracted with chloroform washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =3:2) and dried to give 1.90 g of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

[0241]¹H-NMR(CDCl₃, TMS) δ(ppm): 13.65(1H,d,J=11.2Hz), 7.2-7.5(5H,m), 6.9-7.2(5H, m), 6.76(1H,d,J=8.2Hz), 6.63(1H,d,J=1.88Hz), 6.52(1H,dd,J=8.1,1.9Hz), 5.28(2H,d, J=7.6Hz), 5.14(2H,s), 4.2-4.4(1H,d), 3.83(3H,s), 3.6-3.8(2H,m), 2.35(3H,s), 1.11(3H,d, J=6.5Hz)

[0242] 1.90 g (4.41 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide, 0.99 g (17.6 mmol) of 10% aqueous potassium hydroxide solution, 716 mg (2.20 mmol) of tetrabutylammonium bromide and 20 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature to 50° C. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis, the reaction mixture was cooled. Then, 5% hydrochrolic acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to give 1.80 g of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl) acrylamide.

[0243]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 7.0-7.2(4H,m), 6.7-6.9(4H,m), 6.63 (1H,dd,J=8.0,1.8Hz), 6.30(1H,t,J=71.7Hz), 5.79(1H,d,J=8.1Hz), 5.13(2H,s), 4.3-4.6(1H,m), 3.83(3H,s), 2.6-2.9(2H,m), 2.33(3H,s), 1.18(3H,d,J=6.6Hz)

[0244] 1.80 g (3.74 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide, 693 mg (4.11 mmol) of 48% hydrobromic acid and 20 ml of acetic acid were mixed and stirred at 80° C. for 2 hours. The solvent was distilled off from the reaction mixture under reduced pressure and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 1.10 g of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acrylamide.

[0245]¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.6-6.9(4H,m), 6.37(1H,t, J=71.5Hz), 5.79(1H,d,J=7.7Hz), 5.58(1H,s), 4.3-4.5(1H,m), 3.82(3H,s), 2.6-2.9(2H,m), 2.34(3H,s), 1.18(3H,d,J=6.5Hz)

[0246] Examples of the present compounds are given with their compound numbers below.

[0247] Compound given by formula [I]:

Nos. R¹X Ar Y R² A Z¹ Z² 1001 CH₂FO C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1002 CHF₂O C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1003 CF₃O C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1004 CH₂FO 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1005 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1006 CF₃O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1007 CH₂FO 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1008 CHF₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1009 CF₃O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1010 CH₂FO 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1011 CHF₂O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1012 CF₃O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1013 CH₂FO 4-FC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1014 CHF₂O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1015 CF₃O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1016 CH₂FO 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1017 CHF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1018 CF₃O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1019 CH₂PO 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1020 CHF₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1021 CF₃O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1022 CH₂FO 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1023 CHF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1024 CF₃O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1025 CH₂PO 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1026 CHF₂O 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1027 CF₃O 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1028 CH₂FO 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1029 CHF₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1030 CF₃O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1031 CH₂FO 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1032 CHF₂O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1033 CF₃O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1034 CH₂FO 3-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1035 CHF₂O 3-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1036 CF₃O 3-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1037 CH₂FO 3-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1038 CHF₂O 3-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1039 CF₃O 3-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1040 CH₂FO 3-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1041 CHF₂O 3-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1042 CF₃O 3-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1043 CH₂FO 3-FC₆H₄ O H CH₂CH₂ CH₃O CH3Q 1044 CHF₂O 3-FC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1045 CF₃O 3-FC₆H₄ O H CH₂CH₂ CH3Q CH₃O 1046 CH₂FO 3-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1047 CHF₂O 3-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1048 CF₃O 3-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1049 CH₂FO 3-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1050 CHF₂O 3-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1051 CF₃O 3-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1052 CH₂FO 3-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1053 CHF₂O 3-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1054 CF₃O 3-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1055 CH₂FO 3-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1056 CHF₂O 3-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1057 CF₃O 3-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1058 CH₂FO 3-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1059 CHF₂O 3-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1060 CF₃O 3-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1061 CH₂FO 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1062 CHF₂O 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1063 CF₃O 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1064 CH₂FO 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1065 CHF₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1066 CF₃O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1067 CH₂FO 3,4-Br₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1068 CHF₂O 3,4-Br₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1069 CF₃O 3,4-Br₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1070 CH₂FO 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1071 CHF₂O 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1072 CF₃O 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1073 CH₂FO 3,4-(CH₃O)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1074 CHF₂O 3,4-(CH₃O)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1075 CF₃O 3,4-(CH₃O)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1076 CH₂FO 3,4-(CF₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1077 CHF₂O 3,4-(CF₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1078 CF₃O 3,4-(CF₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1079 CH₂FO 4-Cl-3-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1080 CHF₂O 4-Cl-3-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1081 CF₃O 4-Cl-3-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1082 CH₂FO 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1083 CHF₂O 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1084 CF₃O 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1085 CH₂FO 4-Cl-3-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1086 CHF₂O 4-Cl-3-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1087 CF₃O 4-Cl-3-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1088 CH₂FO 3-Cl-4-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1089 CHF₂O 3-Cl-4-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1090 CF₃O 3-Cl-4-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1091 CH₂FO 3,4-(OCH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1092 CHF₂O 3,4-(OCH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1093 CF₃O 3,4-(OCH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1094 CH₂FO 3,4-(OCH₂CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1095 CHF₂O 3,4-(OCH2CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1096 CF₃O 3,4-(OCH₂CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1097 CH₂FO 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1098 CHF₂O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1099 CF₃O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1100 CH₂FO 3,4-(CH₂)₃3C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1101 CHF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1102 CF₃O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1103 CH₂FO 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1104 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1105 CF₃O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1106 CH₂FO 3,4-(CH₂)₅C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1107 CHF₂O 3,4-(CH₂)₅C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1108 CF₃O 3,4-(CH₂)₅C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1109 CH₂FO C₆H₅ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1110 CHF₂O C₆H₅ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1111 CF₃O C₆H₅ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1112 CH₂FO 4-CH₃C₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1113 CHF₂O 4-CH₃C₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1114 CF₃O 4-CH₃C₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1115 CH₂FO 4-ClC₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1116 CHF₂O 4-ClC₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1117 CF₃O 4-ClC₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1118 CH₂FO 3,4-(OCF₂O)C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1119 CHF₂O 3,4-(OCF₂O)C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1120 CF₃O 3,4-(OCF₂O)C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1121 CH₂FO 3,4-(CH₂)₃C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1122 CHF₂O 3,4-(CH₂)₃C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1123 CF₃O 3,4-(CH₂)₃C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1124 CH₂FO 3,4-(CH₂)₄C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1125 CHF₂O 3,4-(CH₂)₄C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1126 CF₃O 3,4-(CH₂)₄C₆H₃ O H CH(CH₃)CH₂ CH₃O CH₃O 1127 CH₂FO C₆H₅ O H CH₂CH₂ CH₃O C₂H₅O 1128 CHF₂O C₆H₅ O H CH₂CH₂ CH₃O C₂H₅O 1129 CF₃O C₆H₅ O H CH₂CH₂ CH₃O C₂H₅O 1130 CH₂FO 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1131 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1132 CF₃O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1133 CH₂FO 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1134 CHF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1135 CF₃O 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1136 CH₂FO 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1137 CHF₂O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1138 CF₃O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1139 CH₂FO 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1140 CHF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1141 CF₃O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1142 CH₂FO 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1143 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1144 CF₃O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1145 CH₂FO C₆H₅ S H CH₂CH₂ CH₃O CH₃O 1146 CHF₂O C₆H₅ S H CH₂CH₂ CH₃O CH₃O 1147 CF₃O C₆H₅ S H CH₂CH₂ CH₃O CH₃O 1148 CH₂FO 4-CH₃C₆H₄ S H CH₂CH₂ CH₃O CH₃O 1149 CHF₂O 4-CH₃C₆H₄ S H CH₂CH₂ CH₃O CH₃O 1150 CF₃O 4-CH₃C₆H₄ S H CH₂CH₂ CH₃O CH₃O 1151 CH₂FO 4-ClC₆H₄ S H CH₂CH₂ CH₃O CH₃O 1152 CHF₂O 4-ClC₆H₄ S H CH₂CH₂ CH₃O CH₃O 1153 CF₃O 4-ClC₆H₄ S H CH₂CH₂ CH₃O CH₃O 1154 CH₂FO 3,4-(OCF₂O)C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1155 CHF₂O 3,4-(OCF₂O)C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1156 CF₃O 3,4-(OCF₂O)C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1157 CH₂FO 3,4-(CH₂)₃C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1158 CHF₂O 3,4-(CH₂)₃C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1159 CF₃O 3,4-(CH₂)₃C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1160 CH₂FO 3,4-(CH₂)₄C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1161 CHF₂O 3,4-(CH₂)₄C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1162 CF₃O 3,4-(CH₂)₄C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1163 CH₂FS C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1164 CHF₂S C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1165 CF₃S C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1166 CH₂FS 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1167 CHF₂S 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1168 CF₃S 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1169 CH₂FS 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1170 CHF₂S 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1171 CF₃S 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1172 CH₂FS 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1173 CHF₂S 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1174 CF₃S 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1175 CH₂FS 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1176 CHF₂S 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1177 CF₃S 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1178 CH₂FS 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1179 CHF₂S 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1180 CF₃S 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1181 CH≡CCH₂O C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1182 CH≡CCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1183 CH≡CCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1184 CH≡CCH₂O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1185 CH≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1186 CH≡CCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1187 CH≡CCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1188 CH≡CCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1189 CH≡CCH₂O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1190 CH≡CCH₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1191 CH≡CCH₂O 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1192 CH≡CCH₂O 3,4-(OCH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1193 CH≡CCH₂O 3,4-(OCH₂CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1194 CH≡CCH₂O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1195 CH≡CCH₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1196 CH≡CCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1197 CHBrF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1198 CHBrF₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1199 CHBrF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1200 CHBrF₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1201 CHBrF₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1202 CHBrF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1203 CHBrF₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1204 CHBrF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1205 CHBrF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1206 CHClF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1207 CHClF₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1208 CHClF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1209 CHClF₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1210 CHClF₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1211 CHClF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1212 CHClF₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1213 CHClF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1214 CHClF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1215 CCl≡CCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1216 CCl≡CCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1217 CCl≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1218 CCl≡CCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1219 CCl≡CCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1220 CCl≡CCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1221 CCl≡CCH₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1222 CCl≡CCH₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1223 CCl≡CCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1224 CCl₂═CHCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1225 CCl₂═CHCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1226 CCl₂═CHCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1227 CCl₂═CHCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1228 CCl₂═CHCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1229 CCl₂═CHCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1230 CCl₂═CHCH₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1231 CCl₂═CHCH₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1232 CCl₂═CHCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1233 CH₂FCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1234 CH₂FCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1235 CH₂FCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1236 CH₂FCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1237 CH₂FCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1238 CH₂FCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1239 CH₂FCH₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1240 CH₂FCH₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1241 CH₂FCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1242 CClF₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 1243 CBrF₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 1244 CH₂FCH₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 1245 CH≡CCH₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 1246 CH₂FO 4-NO₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1247 CHF₂O 4-NO₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1248 CF₃O 4-NO₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1249 CH═CCH₂O 4-NO₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1250 CH₂FO 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1251 CHF₂O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1252 CF₃O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1253 CH≡CCH₂O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1254 CH₂FO 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH₃O 1255 CHF₂O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH₃O 1256 CF₃O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH₃O 1257 CH≡CCH₂O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH₃O 1258 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃CH₂CH₂O 1259 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O (CH₃)₂CHO 1260 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O cyclopropoxy 1261 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O Cyclopropyl- methoxy 1262 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O butoxy 1263 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O isobutoxy 1264 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O sec-butoxy 1265 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O t-butoxy 1266 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O allyloxy 1267 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 2-butenyloxy 1268 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1269 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 2-butynyloxy 1270 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 2-pentynyl- oxy 1271 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O 1-methyl-2- propynyloxy 1272 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 3-butynyloxy 1273 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 4-pentynyl- oxy 1274 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O NCCH₂O 1275 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃S 1276 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅S 1277 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₂FO 1278 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CHF₂O 1279 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CF₃O 1280 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CF₃CH₂O 1281 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₆H₄CH₂O 1282 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃CO₂ 1283 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅CO₂ 1284 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃OCH₂O 1285 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O ethoxy- methoxy 1286 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃NHCO₂ 1287 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 3,3-dichloro- allyloxy 1288 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 3-chloro-2- propynyl 1289 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃CH₂CH₂O CH₃O 1290 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ (CH₃)₂CHO CH₃O 1291 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ cyclopropoxy CH₃O 1292 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ Cyclopropyl- CH₃O methoxy 1293 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ butoxy CH₃O 1294 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ isobutoxy CH₃O 1295 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ sec-butoxy CH₃O 1296 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ t-butoxy CH₃O 1297 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ allyloxy CH₃O 1298 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 2-butenyl- CH₃O oxy 1299 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH≡CCH₂O CH₃O 1300 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 2-butynyl- CH₃O oxy 1301 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 2-pentynyl CH₃O oxy 1302 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 1-methyl-2- CH₃O propynyloxy 1303 CHF₂O 3,4(CH₂)₄C₆H₃ O H CH₂CH₂ 3-butynyl CH₃O oxy 1304 CHF₂O 3,4(CH₂)₄C₆H₃ O H CH₂CH₂ 4-pentynyl CH₃O oxy 1305 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ NCCH₂O CH₃O 1306 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃S CH₃O 1307 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅S CH₃O 1308 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₂FO CH₃O 1309 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CHF₂O CH₃O 1310 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CF₃O CH₃O 1311 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CF₃CH₂O CH₃O 1312 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ OH CH₃O 1313 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃CO₂ CH₃O 1314 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅CO₂ CH₃O 1315 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃OCH₂O CH₃O 1316 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ ethoxy- CH₃O methoxy 1317 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃NHCO₂ CH₃O 1318 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 3,3-dichloro- CH₃O allyloxy 1319 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 3-chloro-2- CH₃O propynyl 1320 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CH₃O 1321 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O C₂H₅O 1322 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CH₃CH₃CH₃O 1323 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O butoxy 1324 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O allyloxy 1325 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CH≡CCH₂O 1326 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O 2-butynyl oxy 1327 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O 3-butynyl oxy 1328 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O NCCH₂O 1329 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CH₃S 1330 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CF₃O 1331 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy propoxy 1332 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy (CH₃)₂CHO 1333 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy cyclopropyl methoxy 1334 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy butoxy 1335 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy allyloxy 1336 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy CH≡CCH₂O 1337 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy 2-butynyl oxy 1338 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy 3-butynyl oxy 1339 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy NCCH₂O 1340 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy CH₃S 1341 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy CF₃O 1342 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy CCl≡CCH₂O 1343 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ (CH₃)₂CHO CH≡CCH₂O 1344 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ cyclopropyl- CH≡CCH₂O methoxy 1345 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ butoxy CH≡CCH₂O 1346 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ allyloxy CH≡CCH₂O 1347 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH≡CCH₂O CH≡CCH₂O 1348 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 2-butynyl CH≡CCH₂O oxy 1349 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 3-butynyl CH≡CCH₂O oxy 1350 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ NCCH₂O CH≡CCH₂O 1351 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃S CH≡CCH₂O 1352 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CF₃O CH≡CCH₂O 1353 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1354 CHF₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1355 CHF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1356 CHF₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1357 CHF₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1358 CHF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1359 CHF₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1360 CHF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1361 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1362 CH₂FO 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1363 CF₃O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1364 CH≡CCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1365 CH₂FO 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1366 CF₃O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1367 CH≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1368 CH₂FO 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1369 CF₃O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1370 CH≡CCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1371 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O OH 1372 CH₂FO 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1373 CF₃O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1374 CH≡CCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1375 CH₂FO 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1376 CF₃O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1377 CH≡CCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1378 CH₂FO 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1379 CF₃O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1380 CH≡CCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1381 CH₂FO 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1382 CF₃O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1383 CH≡CCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1384 CH₂FO 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1385 CF₃O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1386 CH≡CCH₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1387 CH₂FO C₆H₅ O H CH₂CH₂ CH₃O CH≡CCH₂O 1388 CHF₂O C₆H₅ O H CH₂CH₂ CH₃O CH≡CCH₂O 1389 CF₃O C₆H₅ O H CH₂CH₂ CH₃O CH≡CCH₂O 1390 CH≡CCH₂O C₆H₅ O H CH₂CH₂ CH₃O CH≡CCH₂O 1391 CH₂FO 4-FC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1392 CHF₂O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1393 CF₃O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1394 CH≡CCH₂O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1395 CH₂FO 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1396 CHF₂O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1397 CF₃O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1398 CH≡CCH₂O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1399 CH₂FO 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1400 CHF₂O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1401 CF₃O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1402 CH≡CCH₂O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1403 CH₂FO 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1404 CHF₂O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1405 CF₃O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1406 CH≡CCH₂O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1407 CH₂FO 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1408 CHF₂O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1409 CF₃O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1410 CH≡CCH₂O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1411 CH₂FO 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1412 CHF₂O 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1413 CF₃O 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1414 CH≡CCH₂O 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1415 CH₂FO 4-CH≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1416 CHF₂O 4-CH≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1417 CF₃O 4-CH≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1418 CH≡CCH₂O 4-CH≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1419 CH₂FO 4-N≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1420 CHF₂O 4-N≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1421 CF₃O 4-N≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1422 CH≡CCH₂O 4-N≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1423 CH₂FO 4-CH₂≡CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1424 CHF₂O 4-CH₂≡CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1425 CF₃O 4-CH₂≡CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1426 CH≡CCH₂O 4-CH₂≡CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1427 CHF₂O 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1428 CH≡CCH₂O 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1429 CHF₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1430 CH≡CCH₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1431 CHF₂O 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1432 CH≡CCH₂O 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1433 CHF₂O 3-F-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1434 CH≡CCH₂O 3-F-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1435 CHF₂O 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1436 CH≡CCH₂O 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH2 CH≡CCH₂O 1437 CHF₂O 4-Cl-3-FC₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1438 CH≡CCH₂O 4-Cl-3-FC₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1439 CHF₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1440 CH≡CCH₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1441 CHF₂O 3-Cl-4-CH₃C₆H₃ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1442 CH≡CCH₂O 3-Cl-4-CH₃C₆H₃ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1443 CHF₂O 3,4-Cl₂C₆H₃ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1444 CH≡CCH₂O 3,4-Cl₂C₆H₃ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1445 CHF₂O 4-CH₃C₆H₄ S H CH₂CH₂ CH₃O CH≡CCH₂O 1446 CHF₂O 4-ClC₆H₄ S H CH₂CH₂ CH₃O CH≡CCH₂O 1447 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ Cl CH₃O 1448 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃ CH₃O 1449 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃CH₂ CH₃O 1450 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ OCH₂CH₂O 1451 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₆H₅CH₂O 1452 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O OH 1453 CHF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₆H₅CH₂O 1454 CHF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O OH 1455 CH≡CCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₆H₅CH₂O 1456 CH≡CCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O OH 1457 CH≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₆H₅ CH₂O 1458 CH≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O OH 1459 CHF₂O 4-CH₃C₆H₄ O CH₃ CH₂CH₂ CH₃O CH≡CCH₂O 1460 CHF₂O 4-CH₃C₆H₄ O ethyl CH₂CH₂ CH₃O CH≡CCH₂O 1461 CHF₂O 4-CH₃C₆H₄ O propyl CH₂CH₂ CH₃O CH≡CCH₂O 1462 CHF₂O 4-ClC₆H₄ O CH₃ CH₂CH₂ CH₃O CH≡CCH₂O 1463 CHF₂O 3,4-(CH₂)₄C₆H₃ O CH₃ CH₂CH₂ CH₃O CH≡CCH₂O 1464 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH(CH₃)CH₂ CH₃O CH₃O 1465 CHF₂O 4-CH₃C₆H₄ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1466 CHF₂O 4-ClC₆H₄ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1467 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH(CH₃) CH₃O CH₃O 1468 CHF₂O 4-CH₃C₆H₄ O H CH₂CH(CH₃) CH₃O CH≡CCH₂O 1469 CHF₂O 4-ClC₆H₄ O H CH₂CH(CH₃) CH₃O CH≡CCH₂O 1470 CHF₂O 4-CH₃C₆H₄ O H CH₂CHF CH₃O CH≡CCH₂O 1471 CHF₂O 4-CH₃C₆H₄ O H CH₂CHCl CH₃O CH≡CCH₂O 1472 CHF₂O 4-CH₃C₆H₄ O H CH₂CH(OCH₃) CH₃O CH≡CCH₂O 1473 CHF₂O 4-CH₃C₆H₄ O H CH₂CH(CN) CH₃O CH≡CCH₂O 1474 CHF₂O 4-CH₃C₆H₄ O H CH(CN)CH₂ CH₃O CH≡CCH₂O 1475 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂CH₂ CH₃O CH₃O 1476 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂CH₂ CH₃O CH₃O 1477 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂CH₂ CH₃O CH≡CCH₂O 1478 CHF₂O 4-ClC₆H₄ O H CH₂CH₂CH₂ CH₃O CH≡CCH₂O 2001 CH₂FO 2-thienyl O H CH₂CH₂ CH₃O CH₃O 2002 CHF₂O 2-thienyl O H CH₂CH₂ CH₃O CH₃O 2003 CF₃O 2-thienyl O H CH₂CH₂ CH₃O CH₃O 2004 CH₂FO 3-thienyl O H CH₂CH₂ CH₃O CH₃O 2005 CHF₂O 3-thienyl O H CH₂CH₂ CH₃O CH₃O 2006 CF₃O 3-thienyl O H CH₂CH₂ CH₃O CH₃O 2007 CH₂FO 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2008 CHF₂O 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2009 CF₃O 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2010 CH₂FO 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2011 CHF₂O 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2012 CF₃O 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2013 CH₂FO 2-(4-chlorothienyl) O H CH₂CH₂ CH₃O CH₃O 2014 CHF₂O 2-(4-chlorothienyl) O H CH₂CH₂ CH₃O CH₃O 2015 CF₃O 2-(4-chlorothienyl) O H CH₂CH₂ CH₃O CH₃O 2016 CH₂FO 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O thienyl) 2017 CHF₂O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O thienyl) 2018 CF₃O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O thienyl) 2019 CH₂FO 2-furyl O H CH₂CH₂ CH₃O CH₃O 2020 CHF₂O 2-furyl O H CH₂CH₂ CH₃O CH₃O 2021 CF₃O 2-furyl O H CH₂CH₂ CH₃O CH₃O 2022 CH₂FO 3-furyl O H CH₂CH₂ CH₃O CH₃O 2023 CHF₂O 3-furyl O H CH₂CH₂ CH₃O CH₃O 2024 CF₃O 3-furyl O H CH₂CH₂ CH₃O CH₃O 2025 CH₂FO 2-(5-methyfuryl) O H CH₂CH₂ CH₃O CH₃O 2026 CHF₂O 2-(5-methyfuryl) O H CH₂CH₂ CH₃O CH₃O 2027 CF₃O 2-(5-methyfuryl) O H CH₂CH₂ CH₃O CH₃O 2028 CH₂FO 2-pyridyl O H CH₂CH₂ CH₃O CH₃O 2029 CHF₂O 2-pyridyl O H CH₂CH₂ CH₃O CH₃O 2030 CF₃O 2-pyridyl O H CH₂CH₂ CH₃O CH₃O 2031 CH₂FO 2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH₃O 2032 CHF₂O 2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH₃O 2033 CF₃O 2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH₃O 2034 CH₂FO 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O pyridyl) 2035 CHF₂O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O pyridyl) 2036 CF₃O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O pyridyl) 2037 CH₂FO 2-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2038 CHF₂O 2-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2039 CF₃O 2-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2040 CH₂FO 4-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2041 CHF₂O 4-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2042 CF₃O 4-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2043 CH₂FO 2-pyrazinyl O H CH₂CH₂ CH₃O CH₃O 2044 CHF₂O 2-pyrazinyl O H CH₂CH₂ CH₃O CH₃O 2045 CF₃O 2-pyrazinyl O H CH₂CH₂ CH₃O CH₃O 2046 CH₂FO 2-thiazolyl O H CH₂CH₂ CH₃O CH₃O 2047 CHF₂O 2-thiazolyl O H CH₂CH₂ CH₃O CH₃O 2048 CF₃O 2-thiazolyl O H CH₂CH₂ CH₃O CH₃O 2049 CH₂FO 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2050 CHF₂O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2051 CF₃O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2052 CH₂FO 2-(3-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2053 CHF₂O 2-(3-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2054 CF₃O 2-(3-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2055 CH₂FO 1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH₃O 2056 CHF₂O 1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH₃O 2057 CF₃O 1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH₃O 2058 CH₂FO 2-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2059 CHF₂O 2-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2060 CF₃O 2-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2061 CH₂FO 3-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2062 CHF₂O 3-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2063 CF₃O 3-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2064 CH₂FO 2-thienyl S H CH₂CH₂ CH₃O CH₃O 2065 CHF₂O 2-thienyl S H CH₂CH₂ CH₃O CH₃O 2066 CF₃O 2-thienyl S H CH₂CH₂ CH₃O CH₃O 2067 CH₂FO 3-thienyl S H CH₂CH₂ CH₃O CH₃O 2068 CHF₂O 3-thienyl S H CH₂CH₂ CH₃O CH₃O 2069 CF₃O 3-thienyl S H CH₂CH₂ CH₃O CH₃O 2070 CH₂FO 2-(5-methylpyridyl) O H CH₂CH₂ CH₃CH₂O CH₃O 2071 CHF₂O 2-(5-methylpyridyl) O H CH₂CH₂ CH₃CH₂O CH₃O 2072 CF₃O 2-(5methylpyridyl) O H CH₂CH₂ CH₃CH₂O CH₃O 2073 CH₂FO 1-naphthyl O H CH₂CH₂ CH₃O CH₃O 2074 CHF₂O 1-naphthyl O H CH₂CH₂ CH₃O CH₃O 2075 CF₃O 1-naphthyl O H CH₂CH₂ CH₃O CH₃O 2076 CH₂FO 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 2077 CHF₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 2078 CF₃O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 2079 CH₂FO 2-naplithyl S H CH₂CH₂ CH₃O CH₃O 2080 CHF₂O 2-naphthyl S H CH₂CH₂ CH₃O CH₃O 2081 CF₃O 2-naphthyl S H CH₂CH₂ CH₃O CH₃O 2082 CH₂FO 5-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2083 CHF₂O 5-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2084 CF₃O 5-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2085 CH₂FO 6-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2086 CHF₂O 6-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2087 CF₃O 6-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2088 CH₂FO 5-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2089 CHF₂O 5-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2090 CF₃O 5-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2091 CH₂FO 6-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2092 CHF₂O 6-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2093 CF₃O 6-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2094 CH₂FO 5-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2095 CHF₂O 5-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2096 CF₃O 5-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2097 CH₂FO 6-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2098 CHF₂O 6-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2099 CF₃O 6-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2100 CH₂FO 2-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2101 CHF₂O 2-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2102 CF₃O 2-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2103 CH₂FO 2-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2104 CHF₂O 2-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2105 CF₃O 2-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2106 CH₂FO 2-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2107 CHF₂O 2-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2108 CF₃O 2-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2109 CH₂FO 3-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2110 CHF₂O 3-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2111 CF₃O 3-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2112 CH₂FO benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH₃O 5-yl 2113 CHF₂O benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH₃O 5-yl 2114 CF₃O benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH₃O 5-yl 2115 CH₂FO 2-benzimidazolyl O H CH₂CH₂ CH₃O CH₃O 2116 CHF₂O 2-benzimidazolyl O H CH₂CH₂ CH₃O CH₃O 2117 CF₃O 2-benzimidazolyl O H CH₂CH₂ CH₃O CH₃O 2118 CH₂FO 2-(1-methylbenzimi- O H CH₂CH₂ CH₃O CH₃O dazolyl) 2119 CHF₂O 2-(1-methylbenzimi- O H CH₂CH₂ CH₃O CH₃O dazolyl) 2120 CF₃O 2-(1-methylbenzimi- O H CH₂CH₂ CH₃O CH₃O dazolyl) 2121 CH≡CCH₂O 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2122 CH≡CCH₂O 2-(5-trifluorometh- O H CH₂CH₂ CH₃O CH₃O ylthienyl) 2123 CH≡CCH₂O 2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH₃O 2124 CH≡CCH₂O 2-(5-trifluorometh- O H CH₂CH₂ CH₃O CH₃O ylpyridyl) 2125 CH≡CCH₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 2126 CH₂FO 2-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2127 CHF₂O 2-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2128 CF₃O 2-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2129 CH₂FO 3-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2130 CHF₂O 3-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2131 CF₃O 3-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2132 CH₂FO 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2133 CHF₂O 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2134 CF₃O 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2135 CH₂FO 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2136 CHF₂O 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2137 CF₃O 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2138 CH₂FO 2-(5-chlorothienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2139 CHF₂O 2-(5-chlorothienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2140 CF₃O 2-(5-chlorothienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2141 CH₂FO 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O thienyl) 2142 CHF₂O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O thienyl) 2143 CF₃O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O thienyl) 2144 CH₂FO 2-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2145 CHF₂O 2-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2146 CF₃O 2-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2147 CH₂FO 3-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2148 CHF₂O 3-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2149 CF₃O 3-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2150 CH₂FO 2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2151 CHF₂O 2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2152 CF₃O 2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2153 CH₂FO 2-pyridyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2154 CHF₂O 2-pyridyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2155 CF₃O 2-pyridyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2156 CH₂FO 2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2157 CHF₂O 2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2158 CF₃O 2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2159 CH₂FO 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O pyridyl) 2160 CHF₂O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O pyridyl) 2161 CF₃O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O pyridyl) 2162 CH₂FO 2-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2163 CHF₂O 2-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2164 CF₃O 2-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2165 CH₂FO 4-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2166 CHF₂O 4-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2167 CF₃O 4-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2168 CH₂FO 2-pyrazinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2169 CHF₂O 2-pyrazinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2170 CF₃O 2-pyrazinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2171 CH₂FO 2-thiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2172 CHF₂O 2-thiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2173 CF₃O 2-thiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2174 CH₂FO 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2175 CHF₂O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2176 CF₃O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2177 CH₂FO 3-(3-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2178 CHF₂O 3-(3-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2179 CF₃O 3-(3-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2180 CH₂FO 1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2181 CHF₂O 1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2182 CF₃O 1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2183 CH₂FO 2-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2184 CHF₂O 2-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2185 CF₃O 2-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2186 CH₂FO 3-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2187 CHF₂O 3-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2188 CF₃O 3-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2189 CH₂FO 2-naphthyl O H CH(CH₃)CH₂ CH₃O CH₃O 2190 CHF₂O 2-naphthyl O H CH(CH₃)CH₂ CH₃O CH₃O 2191 CF₃O 2-naphthyl O H CH(CH₃)CH₂ CH₃O CH₃O 2192 CH₂FO 2-naphthyl O CH₃ CH₂CH₂ CH₃O CH₃O 2193 CHF₂O 2-naphthyl O CH₃ CH₂CH₂ CH₃O CH₃O 2194 CF₃O 2-naphthyl O CH₃ CH₂CH₂ CH₃O CH₃O 2195 CH₂FO 2-thienyl O CH₃ CH₂CH₂ CH₃O CH₃O 2196 CHF₂O 2-thienyl O CH₃ CH₂CH₂ CH₃O CH₃O 2197 CF₃O 2-thienyl O CH₃ CH₂CH₂ CH₃O CH₃O 2198 CH₂FO 1-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2199 CHF₂O 1-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2200 CF₃O 1-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2201 CH₂FO 2-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2202 CHF₂O 2-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2203 CF₃O 2-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2204 CH₂FO 2-naphthyl S H CH₂CH₂ CH₃O CH≡CCH₂O 2205 CHF₂O 2-naphthyl S H CH₂CH₂ CH₃O CH≡CCH₂O 2206 CF₃O 2-naphthyl S H CH₂CH₂ CH₃OCH₂ CH≡CCH₂O 2207 CH₂FO 5-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2208 CHF₂O 5-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2209 CF₃O 5-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2210 CH₂FO 6-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2211 CHF₂O 6-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2212 CF₃O 6-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2213 CH₂FO 5-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2214 CHF₂O 5-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2215 CF₃O 5-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2216 CH₂FO 6-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2217 CHF₂O 6-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2218 CF₃O 6-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2219 CH₂FO 5-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2220 CHF₂O 5-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2221 CF₃O 5-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2222 CH₂FO 6-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2223 CHF₂O 6-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2224 CF₃O 6-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2225 CH₂FO 2-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2226 CHF₂O 2-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2227 CF₃O 2-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2228 CH₂FO 2-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2229 CHF₂O 2-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2230 CF₃O 2-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2231 CH₂FO 3-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2232 CHF₂O 3-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2233 CF₃O 3-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2234 CH₂FO 2-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2235 CHF₂O 2-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2236 CF₃O 2-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2237 CH₂FO 3-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2238 CHF₂O 3-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2239 CF₃O 3-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2240 CH₂FO benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH≡CCH₂O 5-yl 2241 CHF₂O benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH≡CCH₂O 5-yl 2242 CF₃O benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH≡CCH₂O 5-yl 2243 CH₂FO 2-benzimidazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2244 CHF₂O 2-benzimidazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2245 CF₃O 2-benzimidazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2246 CF₃S 2-thienyl O H CH₂CH₂ CH₃O CH₃O 2247 CH₂FO 2-(1-methylbenzimidazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2248 CHF₂O 2-(1-methylbenzimidazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2249 CF₃O 2-(1-methylbenzimidazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2250 CH≡CCH₂O 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2251 CH≡CCH₂O 2-(5-trifluoromethyl O H CH₂CH₂CH₃O CH₃O thienyl) 2252 CH≡CCH₂O 2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH₃O 2253 CH≡CCH₂O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O pyridyl) 2254 CH≡CCH₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O

[0248] Formulation examples are given below. Parts represent parts by weight. The numbers of the present compounds are represented by the above-mentioned numbers.

Formulation Example 1

[0249] Fifty parts of each of the present compounds 1001-1478 and 2001-2254, 3 parts of calcium ligninsulfonate, 2 parts of magnesium laurylsulfate and 45 parts of synthetic hydrated silica are pulverized and mixed well to give wettable powders of each compound.

Formulation Example 2

[0250] Twenty parts of each of the present compounds 1001-1478 and 2001-2254 and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and wet-pulverized finely. To the obtained mixture, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminium magnesium silicate is added and further 10 parts of propylene glycol are added to give a flowable of each compound.

Formulation Example 3

[0251] Two parts of each of the present compounds 1001-1478 and 2001-2254, 88 parts of kaolin clay and 10 parts of talc are pulverized and mixed well to give dusts of each compound.

Formulation Example 4

[0252] Five parts of each of the present compounds 1001-1478 and 2001-2254, 14 parts of polyoxyethylenestyryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene are mixed well to give emulsifiable concentrates of each compound.

Formulation Example 5

[0253] Two parts of each of the present compounds 1001-1478 and 2001-2254, 1 part of synthetic hydrated silica, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay are pulverized and mixed well, and water is added thereto and kneeded, granulated and dried to give granules of each compound.

Formulation Example 6

[0254] Ten parts of each of the present compounds 1001-1478 and 2001-2254, 35 parts of white carbon (calsium silicate) containing 50% of ammonium polyoxyethylenealkyl ether sulfate and 55 parts of water are mixed and wet pulverized finely to give a flowable of each compound.

[0255] Next, usefulness of the present compounds for controlling plant diseases is shown by test examples. The present compounds are represented by the numbers referred to in the above table.

[0256] The control effect of the present compounds was evaluated by visually observing the area of a lesion on a sample plant in investigation and comparing the area of a lesion in a non-treatment district and the area of a lesion in a district treated with the present compound.

Test Example 1

[0257] Sand loam was compacted in a plastic pot, a grape (variety: Berry A) was seeded and grown in a green house for 40 days. The present compounds 1004, 1005, 1006, 1016, 1017, 1020, 1023, 1026, 1029, 1065, 1103, 1104, 1143, 1160, 1182, 1196, 1197, 1223, 1232, 1241, 1251, 1258, 1266, 1268, 1271, 1274, 1281, 1282, 1305, 1320, 1371, 2077 and 2133 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (200 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Plasmopara viticola was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 6 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Test Example 2

[0258] Sand loam was compacted in a plastic pot, a grape (variety: Berry A) was seeded and grown in a green house for 40 days. The present compounds 1259, 1284, 1353, 1355, 1360, 1367, 1445, 1447 and 1450 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (50 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Plasmopara viticola was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 6 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Test Example 3

[0259] Sand loam was compacted in a plastic pot, a grape (variety: Berry A) was seeded and grown in a green house for 40 days. The present compounds 1354, 1357, 1358, 1364, 1388, 1392, 1429 and 2202 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (12.5 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Plasmopara viticola was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 6 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Test Example 4

[0260] Sand loam was compacted in a plastic pot, a tomato (variety: Ponterosa) was seeded and grown in a green house for 20 days. The present compounds 1004, 1005, 1006, 1016, 1017, 1020, 1023, 1026, 1029, 1034, 1065, 1103, 1104, 1122, 1143, 1160, 1182, 1185, 1196, 1197, 1223, 1124, 1127, 1232, 1241, 1251, 1258, 1259, 1268, 1269, 1274, 1281, 1282, 1284, 1299, 1320, 1353, 1354, 1358, 1360, 1388, 1367, 1392, 1429, 1445, 1448, 1450, 1465, 1476, 2077 and 2133 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (500 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of tomato leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Phytophthora infestans was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 4 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Industrial Applicability

[0261] The present compound has an excellent efficacy for controlling plant diseases and is useful as an active ingredient of fungicide, especially agricultural and horticultural fungicide. 

1. An amide compound given by formula [I]:

wherein R¹ represents a C1-C10 haloalkyl group, C2-C10 haloalkenyl group, C3-C10 haloalkynyl group, C3-C8 halocycloalkyl group or C3-C10 alkynyl group; R² represents a hydrogen atom or C1-C3 alkyl group; X represents an oxygen atom or sulfur atom; Y represents an oxygen atom or sulfur atom; Ar represents an aromatic group; A represents an ethylene group or trimethylene group, said ethylene group and trimethylene group may be substituted by one or more selected from halogen atom, amino group, hydroxy group, cyano group, nitro group, C1-C6 alkyl group, C3-C6 cycloalkyl group, C3-C6 cycloalkenyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group, C2-C6 (alkoxycarbonyl) group and tri(C1-C6 alkyl)silyl group; Z¹ and Z² are the same or different and represents a halogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C6 cycloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C2-C6 (alkoxyalkoxy) group, C4-C6 (cycloalkylalkoxy) group, C3-C6 alkenyloxy group, C3-C6 haloalkenyloxy group, C3-C6 alkynyloxy group, C3-C6 haloalkynyloxy group, C3-C6 cycloalkoxy group, C3-C6 cycloalkenyloxy group, cyano C1-C5 alkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group, (C1-C5 alkoxy)carbonyl group, phenoxy group, benzyloxy group, hydroxy group or cyano group, the benzene ring of said phenyl group and benzyloxy group may be substituted by one or more selected from halogen atom, C1-C6 alkyl group, C1-C6 alkoxy group, trfluoromethyl group, amino group and nitro group; and Z¹ and Z² may represents C2-C6 alkylenedioxy group together.
 2. An amide compound according to claim 1, wherein Ar is an aromatic hydrocarbyl group or aromatic heterocyclic group which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.
 3. An amide compound according to claim 2, wherein Ar is phenyl, naphthyl, thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolidinyl, benzofuryl, benzothienyl, indolyl, benzothiazolyl, benzimidazolyl, benzopyrazolyl, quinolyl, isoquinolyl, pyrazolopyrimidinyl, imidazopyrimidinyl, thiophenopyrimidinyl, thiazolopyrimidinyl, pyrazolopyridyl, imidazopyridyl, thiophenopyridyl or thiazolopyridyl which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.
 4. An amide compound according to claim 2, wherein Ar is phenyl or naphthyl which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.
 5. An amide compound according to claim 2, wherein Ar is phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 3,4-tetramethylenephenyl, 3,4-trimethylenephenyl, 3,4-dichlorophenyl, 3,4-dimethoxyphenyl or 2-naphthyl.
 6. An amide compound according to claim 1, wherein A is an ethylene group.
 7. An amide compound according to claim 1, wherein R² is a hydrogen atom.
 8. An amide compound according to claim 1, wherein both of X and Y are oxygen atoms.
 9. An amide compound according to claim 1, wherein both of Z¹ and Z² are methoxy.
 10. An amide compound according to claim 1, wherein Z¹ is methoxy and Z² is 2-propynyloxy.
 11. An amide compound according to claim 1, wherein R¹ is a fluoromethyl, difluoromethyl, trifluoromethyl or 2-propynyl.
 12. An amide compound according to claim 1, which is N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-[2-(5,6,7,8-tetrahydronaphthalen-2-yl)]acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-methyphenyl) acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2- (4-chlorophenyl) acrylamide or N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide
 13. A fungicide which is characterized by comprising an amide compound described in claim 1 as an active ingredient, and a carrier.
 14. A method for controlling plant diseases which is characterized by applying an effective amount of an amide compound described in claim 1 to plants. 